Macrocyclic picolinamide compounds with fungicidal activity

ABSTRACT

The invention relates to compounds of macrocyclic picolinamides of Formula I suitable to control or prevent growth of fungi.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 61/885,380, and U.S. Provisional Patent ApplicationSer. No. 61/885,391, each filed Oct. 1, 2013, the disclosure of each ofwhich is expressly incorporated by reference herein

BACKGROUND & SUMMARY

Fungicides are compounds, of natural or synthetic origin, which act toprotect and/or cure plants against damage caused by agriculturallyrelevant fungi. Generally, no single fungicide is useful in allsituations. Consequently, research is ongoing to produce fungicides thatmay have better performance, are easier to use, and cost less.

The present disclosure relates to macrocyclic picolinamides and theiruse as fungicides. The compounds of the present disclosure may offerprotection against ascomycetes, basidiomycetes, deuteromycetes andoomycetes.

One embodiment of the present disclosure may include compounds ofFormula I:

X is H or C(O)R₃;

Y is H, C(O)R₃, or Q;

Q is

R₁ is H, alkyl, alkenyl, aryl, —Si(R₆)₃, —C(O)R₆, each substituted with0, 1 or multiple R₅;

R₂ is H, alkyl, aryl, heteroaryl, arylalkyl, each substituted with 0, 1or multiple R₅;

R₃ is alkoxy, benzyloxy, each substituted with 0, 1, or multiple R₅;

R₄ is H, —C(O)R₇, or —CH₂OC(O)R₇;

R₅ is H, alkyl, alkenyl, halo, haloalkyl, alkoxy, aryl, heteroaryl,heterocyclyl, —C(O)R₆;

R₆ is alkyl, alkenyl, haloalkyl, alkoxy, aryl or heteroaryl; and

R₇ is alkyl or alkoxy, each substituted with 0, 1, or multiple R₆;

with the proviso that R₂ is not unsubstituted phenyl or unsubstitutedcyclohexyl.

Another embodiment of the present disclosure may include a fungicidalcomposition for the control or prevention of fungal attack comprisingthe compounds described above and a phytologically acceptable carriermaterial.

Yet another embodiment of the present disclosure may include a methodfor the control or prevention of fungal attack on a plant, the methodincluding the steps of applying a fungicidally effective amount of oneor more of the compounds described above to at least one of the fungus,the plant, and an area adjacent to the plant.

It will be understood by the those skilled in the art that the followingterms may include generic “R”-groups within their definitions, e.g.,“the term alkoxy refers to an —OR substituent”. It is also understoodthat within the definitions for the following terms, these “R” groupsare included for illustration purposes and should not be construed aslimiting or being limited by substitutions about Formula I.

The term “alkyl” refers to a branched, unbranched, or saturated cycliccarbon chain, including, but not limited to, methyl, ethyl, propyl,butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl and the like.

The term “alkenyl” refers to a branched, unbranched or cyclic carbonchain containing one or more double bonds including, but not limited to,ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl,cyclopentenyl, cyclohexenyl, and the like.

The term “alkynyl” refers to a branched or unbranched carbon chaincontaining one or more triple bonds including, but not limited to,propynyl, butynyl and the like.

The term “aryl” refers to any aromatic, mono- or bi-cyclic, containing 0heteroatoms.

The term “unsubstituted phenyl” refers to a phenyl ring in which the 5available bonding sites are all occupied by a hydrogen atom.

The term “unsubstituted cyclohexyl” refers to a 6-membered, saturatedcarbocycle in which the 11 available bonding sites are all occupied by ahydrogen atom.

The term “heterocycle” refers to any aromatic or non-aromatic ring,mono- or bi-cyclic, containing one or more heteroatoms.

The term “alkoxy” refers to an —OR substituent.

The term “cyano” refers to a —C≡N substituent.

The term “hydroxyl” refers to an —OH substituent.

The term “amino” refers to a —NH₂ substituent.

The term “arylalkoxy” refers to —O(CH₂)_(n)—Ar where n is an integerselected from the list 1, 2, 3, 4, 5, or 6.

The term “haloalkoxy” refers to an —OR—X substituent, wherein X is Cl,F, Br, or I, or any combination thereof.

The term “haloalkyl” refers to an alkyl, which is substituted with Cl,F, I, or Br or any combination thereof.

The term “halogen” or “halo” refers to one or more halogen atoms,defined as F, Cl, Br, and I.

The term “nitro” refers to a —NO₂ substituent.

Throughout the disclosure, reference to the compounds of Formula I isread as also including diastereomers, enantiomers, and mixtures thereof.In another embodiment, Formula (I) is read as also including salts orhydrates thereof. Exemplary salts include, but are not limited to:hydrochloride, hydrobromide, and hydroiodide.

It is also understood by those skilled in the art that additionalsubstitution is allowable, unless otherwise noted, as long as the rulesof chemical bonding and strain energy are satisfied and the productstill exhibits fungicidal activity.

Another embodiment of the present disclosure is a use of a compound ofFormula I, for protection of a plant against attack by a phytopathogenicorganism or the treatment of a plant infested by a phytopathogenicorganism, comprising the application of a compound of Formula I, or acomposition comprising the compound to soil, a plant, a part of a plant,foliage, and/or roots.

Additionally, another embodiment of the present disclosure is acomposition useful for protecting a plant against attack by aphytopathogenic organism and/or treatment of a plant infested by aphytopathogenic organism comprising a compound of Formula I and aphytologically acceptable carrier material.

DETAILED DESCRIPTION

The compounds of the present disclosure may be applied by any of avariety of known techniques, either as the compounds or as formulationscomprising the compounds. For example, the compounds may be applied tothe roots or foliage of plants for the control of various fungi, withoutdamaging the commercial value of the plants. The materials may beapplied in the form of any of the generally used formulation types, forexample, as solutions, dusts, wettable powders, flowable concentrate, oremulsifiable concentrates.

Preferably, the compounds of the present disclosure are applied in theform of a formulation, comprising one or more of the compounds ofFormula I with a phytologically acceptable carrier. Concentratedformulations may be dispersed in water, or other liquids, forapplication, or formulations may be dust-like or granular, which maythen be applied without further treatment. The formulations can beprepared according to procedures that are conventional in theagricultural chemical art.

The present disclosure contemplates all vehicles by which one or more ofthe compounds may be formulated for delivery and use as a fungicide.Typically, formulations are applied as aqueous suspensions or emulsions.Such suspensions or emulsions may be produced from water-soluble,water-suspendible, or emulsifiable formulations which are solids,usually known as wettable powders; or liquids, usually known asemulsifiable concentrates, aqueous suspensions, or suspensionconcentrates. As will be readily appreciated, any material to whichthese compounds may be added may be used, provided it yields the desiredutility without significant interference with the activity of thesecompounds as antifungal agents.

Wettable powders, which may be compacted to form water-dispersiblegranules, comprise an intimate mixture of one or more of the compoundsof Formula I, an inert carrier and surfactants. The concentration of thecompound in the wettable powder may be from about 10 percent to about 90percent by weight based on the total weight of the wettable powder, morepreferably about 25 weight percent to about 75 weight percent. In thepreparation of wettable powder formulations, the compounds may becompounded with any finely divided solid, such as prophyllite, talc,chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein,gluten, montmorillonite clays, diatomaceous earths, purified silicatesor the like. In such operations, the finely divided carrier andsurfactants are typically blended with the compound(s) and milled.

Emulsifiable concentrates of the compounds of Formula I may comprise aconvenient concentration, such as from about 1 weight percent to about50 weight percent of the compound, in a suitable liquid, based on thetotal weight of the concentrate. The compounds may be dissolved in aninert carrier, which is either a water-miscible solvent or a mixture ofwater-immiscible organic solvents, and emulsifiers. The concentrates maybe diluted with water and oil to form spray mixtures in the form ofoil-in-water emulsions. Useful organic solvents include aromatics,especially the high-boiling naphthalenic and olefinic portions ofpetroleum such as heavy aromatic naphtha. Other organic solvents mayalso be used, for example, terpenic solvents, including rosinderivatives, aliphatic ketones, such as cyclohexanone, and complexalcohols, such as 2-ethoxyethanol.

Emulsifiers which may be advantageously employed herein may be readilydetermined by those skilled in the art and include various nonionic,anionic, cationic and amphoteric emulsifiers, or a blend of two or moreemulsifiers. Examples of nonionic emulsifiers useful in preparing theemulsifiable concentrates include the polyalkylene glycol ethers andcondensation products of alkyl and aryl phenols, aliphatic alcohols,aliphatic amines or fatty acids with ethylene oxide, propylene oxidessuch as the ethoxylated alkyl phenols and carboxylic esters solubilizedwith the polyol or polyoxyalkylene. Cationic emulsifiers includequaternary ammonium compounds and fatty amine salts. Anionic emulsifiersinclude the oil-soluble salts (e.g., calcium) of alkylaryl sulphonicacids, oil-soluble salts or sulfated polyglycol ethers and appropriatesalts of phosphated polyglycol ether.

Representative organic liquids which may be employed in preparing theemulsifiable concentrates of the compounds of the present disclosure arethe aromatic liquids such as xylene, propyl benzene fractions; or mixednaphthalene fractions, mineral oils, substituted aromatic organicliquids such as dioctyl phthalate; kerosene; dialkyl amides of variousfatty acids, particularly the dimethyl amides of fatty glycols andglycol derivatives such as the n-butyl ether, ethyl ether or methylether of diethylene glycol, the methyl ether of triethylene glycol,petroleum fractions or hydrocarbons such as mineral oil, aromaticsolvents, paraffinic oils, and the like; vegetable oils such as soy beanoil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconutoil, corn oil, cotton seed oil, linseed oil, palm oil, peanut oil,safflower oil, sesame oil, tung oil and the like; esters of the abovevegetable oils; and the like. Mixtures of two or more organic liquidsmay also be employed in the preparation of the emulsifiable concentrate.Organic liquids include xylene, and propyl benzene fractions, withxylene being most preferred in some cases. Surface-active dispersingagents are typically employed in liquid formulations and in an amount offrom 0.1 to 20 percent by weight based on the combined weight of thedispersing agent with one or more of the compounds. The formulations canalso contain other compatible additives, for example, plant growthregulators and other biologically active compounds used in agriculture.

Aqueous suspensions comprise suspensions of one or more water-insolublecompounds of Formula I, dispersed in an aqueous vehicle at aconcentration in the range from about 1 to about 50 weight percent,based on the total weight of the aqueous suspension. Suspensions areprepared by finely grinding one or more of the compounds, and vigorouslymixing the ground material into a vehicle comprised of water andsurfactants chosen from the same types discussed above. Othercomponents, such as inorganic salts and synthetic or natural gums, mayalso be added to increase the density and viscosity of the aqueousvehicle.

The compounds of Formula I can also be applied as granular formulations,which are particularly useful for applications to the soil. Granularformulations generally contain from about 0.5 to about 10 weightpercent, based on the total weight of the granular formulation of thecompound(s), dispersed in an inert carrier which consists entirely or inlarge part of coarsely divided inert material such as attapulgite,bentonite, diatomite, clay or a similar inexpensive substance. Suchformulations are usually prepared by dissolving the compounds in asuitable solvent and applying it to a granular carrier which has beenpreformed to the appropriate particle size, in the range of from about0.5 to about 3 mm. A suitable solvent is a solvent in which the compoundis substantially or completely soluble. Such formulations may also beprepared by making a dough or paste of the carrier and the compound andsolvent, and crushing and drying to obtain the desired granularparticle.

Dusts containing the compounds of Formula I may be prepared byintimately mixing one or more of the compounds in powdered form with asuitable dusty agricultural carrier, such as, for example, kaolin clay,ground volcanic rock, and the like. Dusts can suitably contain fromabout 1 to about 10 weight percent of the compounds, based on the totalweight of the dust.

The formulations may additionally contain adjuvant surfactants toenhance deposition, wetting and penetration of the compounds onto thetarget crop and organism. These adjuvant surfactants may optionally beemployed as a component of the formulation or as a tank mix. The amountof adjuvant surfactant will typically vary from 0.01 to 1.0 percent byvolume, based on a spray-volume of water, preferably 0.05 to 0.5 volumepercent. Suitable adjuvant surfactants include, but are not limited toethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols,salts of the esters or sulphosuccinic acids, ethoxylatedorganosilicones, ethoxylated fatty amines, blends of surfactants withmineral or vegetable oils, crop oil concentrate (mineral oil(85%)+emulsifiers (15%)); nonylphenol ethoxylate;benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleumhydrocarbon, alkyl esters, organic acid, and anionic surfactant; C₉-C₁₁alkylpolyglycoside; phosphated alcohol ethoxylate; natural primaryalcohol (C₁₂-C₁₆) ethoxylate; di-sec-butylphenol EO-PO block copolymer;polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium nitrrate;emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate(8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99. Theformulations may also include oil-in-water emulsions such as thosedisclosed in U.S. patent application Ser. No. 11/495,228, the disclosureof which is expressly incorporated by reference herein.

The formulations may optionally include combinations that contain otherpesticidal compounds. Such additional pesticidal compounds may befungicides, insecticides, herbicides, nematocides, miticides,arthropodicides, bactericides or combinations thereof that arecompatible with the compounds of the present disclosure in the mediumselected for application, and not antagonistic to the activity of thepresent compounds. Accordingly, in such embodiments, the otherpesticidal compound is employed as a supplemental toxicant for the sameor for a different pesticidal use. The compounds of Formula I and thepesticidal compound in the combination can generally be present in aweight ratio of from 1:100 to 100:1.

The compounds of the present disclosure may also be combined with otherfungicides to form fungicidal mixtures and synergistic mixtures thereof.The fungicidal compounds of the present disclosure are often applied inconjunction with one or more other fungicides to control a wider varietyof undesirable diseases. When used in conjunction with otherfungicide(s), the presently claimed compounds may be formulated with theother fungicide(s), tank-mixed with the other fungicide(s) or appliedsequentially with the other fungicide(s). Such other fungicides mayinclude 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol,8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin,Ampelomyces quisqualis, azaconazole, azoxystrobin, Bacillus subtilis,Bacillus subtilis strain QST713, benalaxyl, benomyl,benthiavalicarb-isopropyl, benzylaminobenzene-sulfonate (BABS) salt,bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen,blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole,bupirimate, calcium polysulfide, captafol, captan, carbendazim,carboxin, carpropamid, carvone, chlazafenone, chloroneb, chlorothalonil,chlozolinate, Coniothyrium minitans, copper hydroxide, copper octanoate,copper oxychloride, copper sulfate, copper sulfate (tribasic), cuprousoxide, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil,dazomet, debacarb, diammonium ethylenebis-(dithiocarbamate),dichlofluanid, dichlorophen, diclocymet, diclomezine, dichloran,diethofencarb, difenoconazole, difenzoquat ion, diflumetorim,dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton,dinocap, diphenylamine, dithianon, dodemorph, dodemorph acetate, dodine,dodine free base, edifenphos, enestrobin, enestroburin, epoxiconazole,ethaboxam, ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol,fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil,fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentin acetate,fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumorph,fluopicolide, fluopyram, fluoroimide, fluoxastrobin, fluquinconazole,flusilazole, flusulfamide, flutianil, flutolanil, flutriafol,fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminium,fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acetates,GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalilsulfate, imibenconazole, iminoctadine, iminoctadine triacetate,iminoctadine tris(albesilate), iodocarb, ipconazole, ipfenpyrazolone,iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam,isotianil, kasugamycin, kasugamycin hydrochloride hydrate,kresoxim-methyl, laminarin, mancopper, mancozeb, mandipropamid, maneb,mefenoxam, mepanipyrim, mepronil, meptyl-dinocap, mercuric chloride,mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam,metam-ammonium, metam-potassium, metam-sodium, metconazole,methasulfocarb, methyl iodide, methyl isothiocyanate, metiram,metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam,nitrothal-isopropyl, nuarimol, octhilinone, ofurace, oleic acid (fattyacids), orysastrobin, oxadixyl, oxine-copper, oxpoconazole fumarate,oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen,pentachlorophenol, pentachlorophenyl laurate, penthiopyrad,phenylmercury acetate, phosphonic acid, phthalide, picoxystrobin,polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassiumhydroxyquinoline sulfate, probenazole, prochloraz, procymidone,propamocarb, propamocarb hydrochloride, propiconazole, propineb,proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin,pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox,pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen,quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam,simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodiumpentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, tar oils,tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole,thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl,tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole,tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole,validamycin, valifenalate, valiphenal, vinclozolin, zineb, ziram,zoxamide, Candida oleophila, Fusarium oxysporum, Gliocladium spp.,Phlebiopsis gigantea, Streptomyces griseoviridis, Trichoderma spp.,(RS)—N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide,1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate,1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane,2-(2-heptadecyl-2-imidazolin-1-yl)ethanol,2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide,2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride,2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine,4-(2-nitroprop-1-enyl)phenyl thiocyanateme, ampropylfos, anilazine,azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox,bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl,bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmiumcalcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone,chloraniformethan, chlorfenazole, chlorquinox, climbazole, copperbis(3-phenylsalicylate), copper zinc chromate, cufraneb, cuprichydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram,decafentin, dichlone, dichlozoline, diclobutrazol, dimethirimol,dinocton, dinosulfon, dinoterbon, dipyrithione, ditalimfos, dodicin,drazoxolon, EBP, ESBP, etaconazole, etem, ethirim, fenaminosulf,fenapanil, fenitropan, fluotrimazole, furcarbanil, furconazole,furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin,halacrinate, Hercules 3944, hexylthiofos, ICIA0858, isopamphos,isovaledione, mebenil, mecarbinzid, metazoxolon, methfuroxam,methylmercury dicyandiamide, metsulfovax, milneb, mucochloric anhydride,myclozolin, N-3,5-dichlorophenyl-succinimide,N-3-nitrophenylitaconimide, natamycin,N-ethylmercurio-4-toluenesulfonanilide, nickelbis(dimethyldithiocarbamate), OCH, phenylmercurydimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb;prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyroxychlor,pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole,rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor,thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid,triamiphos, triarimol, triazbutil, trichlamide, urbacid, zarilamid, andany combinations thereof.

Additionally, the compounds described herein may be combined with otherpesticides, including insecticides, nematocides, miticides,arthropodicides, bactericides or combinations thereof that arecompatible with the compounds of the present disclosure in the mediumselected for application, and not antagonistic to the activity of thepresent compounds to form pesticidal mixtures and synergistic mixturesthereof. The fungicidal compounds of the present disclosure may beapplied in conjunction with one or more other pesticides to control awider variety of undesirable pests. When used in conjunction with otherpesticides, the presently claimed compounds may be formulated with theother pesticide(s), tank-mixed with the other pesticide(s) or appliedsequentially with the other pesticide(s). Typical insecticides include,but are not limited to: 1,2-dichloropropane, abamectin, acephate,acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile,alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin,allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan,amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine,athidathion, azadirachtin, azamethiphos, azinphos-ethyl,azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin,bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin,bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron,borax, boric acid, bromfenvinfos, bromocyclen, bromo-DDT, bromophos,bromophos-ethyl, bufencarb, buprofezin, butacarb, butathiofos,butocarboxim, butonate, butoxycarboxim, cadusafos, calcium arsenate,calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran,carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan,cartap, cartap hydrochloride, chlorantraniliprole, chlorbicyclen,chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride,chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron,chlormephos, chloroform, chloropicrin, chlorphoxim, chlorprazophos,chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide,cinerin I, cinerin II, cinerins, cismethrin, cloethocarb, closantel,clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate,copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos,crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate,cyantraniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin,cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran,deltamethrin, demephion, demephion-O, demephion-S, demeton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos,diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos,dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor,dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos,dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran,diofenolan, dioxabenzofos, dioxacarb, dioxathion, disulfoton,dithicrofos, d-limonene, DNOC, DNOC-ammonium, DNOC-potassium,DNOC-sodium, doramectin, ecdysterone, emamectin, emamectin benzoate,EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane,eprinomectin, esdepalléthrine, esfenvalerate, etaphos, ethiofencarb,ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate,ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide,etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor,fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb,fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion,fenthion, fenthion-ethyl, fenvalerate, fipronil, flonicamid,flubendiamide, flucofuron, flucycloxuron, flucythrinate, flufenerim,flufenoxuron, flufenprox, fluvalinate, fonofos, formetanate, formetanatehydrochloride, formothion, formparanate, formparanate hydrochloride,fosmethilan, fospirate, fosthietan, furathiocarb, furethrin,gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD,heptachlor, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon,hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imiprothrin,indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos,isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane,isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos,juvenile hormone I, juvenile hormone II, juvenile hormone III, kelevan,kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos,lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben,mazidox, mecarbam, mecarphon, menazon, mephosfolan, mercurous chloride,mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion,methiocarb, methocrotophos, methomyl, methoprene, methoxychlor,methoxyfenozide, methyl bromide, methyl isothiocyanate,methylchloroform, methylene chloride, metofluthrin, metolcarb,metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime,mipafox, mirex, molosultap, monocrotophos, monomehypo, monosultap,morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine,nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron,noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydeprofos,oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl,penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin,phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor,phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos,pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite,potassium thiocyanate, pp′-DDT, prallethrin, precocene I, precocene II,precocene III, primidophos, profenofos, profluralin, promacyl,promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos,prothoate, protrifenbute, pyraclofos, pyrafluprole, pyrazophos,pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyridaben,pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyrimitate,pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl,quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadilla,schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodiumfluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide,spinetoram, spinosad, spiromesifen, spirotetramat, sulcofuron,sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfurylfluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide,tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, TEPP,terallethrin, terbufos, tetrachloroethane, tetrachlorvinphos,tetramethrin, tetramethylfluthrin, theta-cypermethrin, thiacloprid,thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate,thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium,thiosultap-monosodium, thuringiensin, tolfenpyrad, tralomethrin,transfluthrin, transpermethrin, triarathene, triazamate, triazophos,trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumuron,trimethacarb, triprene, vamidothion, vaniliprole, XMC, xylylcarb,zeta-cypermethrin, zolaprofos, and any combinations thereof.

Additionally, the compounds described herein may be combined withherbicides that are compatible with the compounds of the presentdisclosure in the medium selected for application, and not antagonisticto the activity of the present compounds to form pesticidal mixtures andsynergistic mixtures thereof. The fungicidal compounds of the presentdisclosure may be applied in conjunction with one or more herbicides tocontrol a wide variety of undesirable plants. When used in conjunctionwith herbicides, the presently claimed compounds may be formulated withthe herbicide(s), tank-mixed with the herbicide(s) or appliedsequentially with the herbicide(s). Typical herbicides include, but arenot limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB;2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor,acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim,allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone,amidosulfuron, amino cyclopyrachlor, aminopyralid, amiprofos-methyl,amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton,atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC,beflubutamid, benazolin, bencarbazone, benfluralin, benfuresate,bensulfuron, bensulide, bentazone, benzadox, benzfendizone, benzipram,benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron,bicyclopyrone, bifenox, bilanafos, bispyribac, borax, bromacil,bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon,butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron,butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole,calcium chlorate, calcium cyanamide, cambendichlor, carbasulam,carbetamide, carboxazole chlorprocarb, carfentrazone, CDEA, CEPC,chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine,chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop,chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlornitrofen,chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham,chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin,cinosulfuron, cisanilide, clethodim, cliodinate, clodinafop, clofop,clomazone, clomeprop, cloprop, cloproxydim, clopyralid, cloransulam,CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron,cyanatryn, cyanazine, cycloate, cyclosulfamuron, cycloxydim, cycluron,cyhalofop, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon,dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba,dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P,diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron,difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate,dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano,dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb,dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron,DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon,esprocarb, ethalfluralin, ethametsulfuron, ethidimuron, ethiolate,ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid,etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P,fenoxasulfone, fenteracol, fenthiaprop, fentrazamide, fenuron, ferroussulfate, flamprop, flamprop-M, flazasulfuron, florasulam, fluazifop,fluazifop-P, fluazolate, flucarbazone, flucetosulfuron, fluchloralin,flufenacet, flufenican, flufenpyr, flumetsulam, flumezin, flumiclorac,flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen,fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil,flupropanate, flupyrsulfuron, fluridone, flurochloridone, fluroxypyr,flurtamone, fluthiacet, fomesafen, foramsulfuron, fosamine, furyloxyfen,glufosinate, glufosinate-P, glyphosate, halosafen, halosulfuron,haloxydine, haloxyfop, haloxyfop-P, hexachloroacetone, hexaflurate,hexazinone, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin,imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil,iodomethane, iodosulfuron, ioxynil, ipazine, ipfencarbazone, iprymidam,isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin,isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole,isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron,MAA, MAMA, MCPA, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb,mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam,metamifop, metamitron, metazachlor, metazosulfuron, metflurazon,methabenzthiazuron, methalpropalin, methazole, methiobencarb,methiozolin, methiuron, methometon, methoprotryne, methyl bromide,methyl isothiocyanate, methyldymron, metobenzuron, metobromuron,metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate,monalide, monisouron, monochloroacetic acid, monolinuron, monuron,morfamquat, MSMA, naproanilide, napropamide, naptalam, neburon,nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen,norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene,orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon,oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat,pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol,pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham,phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate,picloram, picolinafen, pinoxaden, piperophos, potassium arsenite,potassium azide, potassium cyanate, pretilachlor, primisulfuron,procyazine, prodiamine, profluazol, profluralin, profoxydim,proglinazine, prometon, prometryn, propachlor, propanil, propaquizafop,propazine, propham, propisochlor, propoxycarbazone, propyrisulfuron,propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor,pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazolynate,pyrazosulfuron, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor,pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac,pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine,quinonamid, quizalofop, quizalofop-P, rhodethanil, rimsulfuron,saflufenacil, S-metolachlor, sebuthylazine, secbumeton, sethoxydim,siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodiumazide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone,sulfometuron, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA,tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim,terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn,tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin,thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb,tiocarbazil, tioclorim, topramezone, tralkoxydim, triafamone,tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, triclopyr,tridiphane, trietazine, trifloxysulfuron, trifluralin, triflusulfuron,trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan,tritac, tritosulfuron, vernolate, and xylachlor.

Another embodiment of the present disclosure is a method for the controlor prevention of fungal attack. This method comprises applying to thesoil, plant, roots, foliage, or locus of the fungus, or to a locus inwhich the infestation is to be prevented (for example applying to cerealor grape plants), a fungicidally effective amount of one or more of thecompounds of Formula 1. The compounds are suitable for treatment ofvarious plants at fungicidal levels, while exhibiting low phytotoxicity.The compounds may be useful both in a protectant and/or an eradicantfashion.

The compounds have been found to have significant fungicidal effectparticularly for agricultural use. Many of the compounds areparticularly effective for use with agricultural crops and horticulturalplants.

It will be understood by those in the art that the efficacy of thecompound for the foregoing fungi establishes the general utility of thecompounds as fungicides.

The compounds have broad ranges of activity against fungal pathogens.Exemplary pathogens may include, but are not limited to, causing agentof wheat leaf blotch (Mycosphaerella graminicola; inperfect stage:Septoria tritici), wheat brown rust (Puccinia triticina), wheat striperust (Puccinia striiformis), scab of apple (Venturia inaequalis),powdery mildew of grapevine (Uncinula necator), barley scald(Rhynchosporium secalis), blast of rice (Magnaporthe grisea), rust ofsoybean (Phakopsora pachyrhizi), glume blotch of wheat (Leptosphaerianodorum), powdery mildew of wheat (Blumeria graminis f.sp. tritici),powdery mildew of barley (Blumeria graminis f.sp. hordei), powderymildew of cucurbits (Erysiphe cichoracearum), anthracnose of cucurbits(Glomerella lagenarium), leaf spot of beet (Cercospora beticola), earlyblight of tomato (Alternaria solani), and spot blotch of barley(Cochliobolus sativus). The exact amount of the active material to beapplied is dependent not only on the specific active material beingapplied, but also on the particular action desired, the fungal speciesto be controlled, and the stage of growth thereof, as well as the partof the plant or other product to be contacted with the compound. Thus,all the compounds, and formulations containing the same, may not beequally effective at similar concentrations or against the same fungalspecies.

The compounds are effective in use with plants in a disease-inhibitingand phytologically acceptable amount. The term “disease-inhibiting andphytologically acceptable amount” refers to an amount of a compound thatkills or inhibits the plant disease for which control is desired, but isnot significantly toxic to the plant. This amount will generally be fromabout 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm beingpreferred. The exact concentration of compound required varies with thefungal disease to be controlled, the type of formulation employed, themethod of application, the particular plant species, climate conditions,and the like. A suitable application rate is typically in the range fromabout 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per squaremeter, g/m²).

Any range or desired value given herein may be extended or alteredwithout losing the effects sought, as is apparent to the skilled personfor an understanding of the teachings herein.

The compounds of Formula I may be made using well-known chemicalprocedures. Intermediates not specifically mentioned in this disclosureare either commercially available, may be made by routes disclosed inthe chemical literature, or may be readily synthesized from commercialstarting materials utilizing standard procedures.

General Schemes

The following schemes illustrate approaches to generating picolinamidecompounds of Formula (I). It may be understood by those skilled in theart that each R₂ may be differentially substituted. The followingdescriptions and examples are provided for illustrative purposes andshould not be construed as limiting in terms of substituents orsubstitution patterns.

Compounds of Formula 1.4, where R₂ is as originally defined, can beprepared according to the methods outlined in Scheme 1, steps a-b.Compounds of Formula 1.2 can be obtained by reaction of an acid chlorideprepared from carboxylic acids of Formula 1.1, where R₂ is as originallydefined, using a chlorinating agent, such as oxalyl chloride or thionylchloride, in a solvent such as dichloroethane (DCE) in the presence of acatalytic amount of N,N-dimethylformamide (DMF), with the amide anion ofa chiral oxazolidinone prepared by treating compound 1.0 withn-butyllithium (n-BuLi) in an anhydrous solvent such as tetrahydrofuran(THF) at −78° C., as shown in a. Compounds of Formula 1.4, can beprepared by treating the boron enolate of compounds of Formula 1.2,formed using dibutyl(((trifluoromethyl)-sulfonyl)oxy)borane and an aminebase such as triethylamine, with a benzyl- or triisopropylsilylprotected lactate-derived aldehyde of Formula 1.3, prepared as describedby Enders et al. Organic Syntheses, 2004, 10, 66; 2002, 78, 177, in asolvent such as dichloromethane (CH₂Cl₂, DCM) at −78° C. to −10° C., asshown in b.

Compounds of Formula 2.6, where R₁ is alkyl, R₂ is as originallydefined, and X is tert-butoxycarbonyl (Boc) can be prepared according tothe methods outlined in Scheme 2, steps a-e. Compounds of Formula 2.1,where R₁ possesses an allylic functionality and R₂ is as originallydefined, can be prepared by treating compounds of Formula 2.0, where R₂is as originally defined, with an allyl carbonate, such astert-butyl(2-methylallyl)carbonate, in the presence of a palladium (0)catalyst with or without the addition of a phosphine ligand, such astris(dibenzylideneacetone)-dipalladium(0) (Pd₂(dba)₃) and1,1′-bis(diphenylphosphino)ferrocene (dppf), in an aprotic solvent suchas THF, at elevated temperatures, such as 45 to 60° C., as depicted ina. Primary alcohols of Formula 2.2, where R₁ possesses an allylicfunctionality and R₂ is as originally defined, can be obtained fromcompounds of Formula 2.1, where R₁ and R₂ are as defined above, bytreatment with a reducing agent such as lithium borohydride (LiBH₄) in amixed solvent system consisting of THF and water (H₂O), as shown in b.Compounds of Formula 2.4, where R₁ possesses an allylic functionalityand R₂ is as originally defined and X is Boc or Cbz, can be preparedfrom compounds of Formula 2.2, where R₁ and R₂ are as defined above, bytreatment with a protected aziridine of Formula 2.3, wherein X is Boc orCbz, such as (S)-1-tert-butyl 2-methyl aziridine-1,2-dicarboxylate, inthe presence of a Lewis acid such as boron trifluoride diethyl etherate(BF₃-Et₂O), in an aprotic solvent such as DCM, as shown in c. Compoundsof Formulas 2.5 or 2.6, wherein the allylic functionality in R₁ has beenreduced to an alkyl functionality, R₂ is as originally defined, and X isBoc, can be prepared from compounds of Formula 2.4, where R₁, R₂, and Xare as defined above, by treatment with hydrogen in the presence of acatalyst, such as palladium on carbon (Pd/C), in a solvent such as ethylacetate (EtOAc), as shown in d. Treating compounds of Formula 2.4, whereR₁, R₂, and X are as defined above and the carboxylic acid is protectedas the benzyl (Bn) ester, as described in d affords compounds of Formula2.6 directly, whereas treatment of compounds of Formula 2.4 wherein thecarboxylic acid is protected as the methyl (Me) ester, as described in daffords compounds of Formula 2.5, which require an additional hydrolysisstep, as shown in e. In step e compounds of Formula 2.5 are converted tocompounds of Formula 2.6, using a hydroxide base, such as lithiumhydroxide (LiOH), in an aqueous THF solvent mixture.

Compounds of Formula 3.5, where R₁ is triisopropylsilyl (TIPS), R₂ is asoriginally defined, and X is as originally defined, but not hydrogen,can be prepared according to the methods outlined in Scheme 3, steps a-fCompounds of Formula 3.1, where R₂ is as originally defined, can beobtained from compounds of Formula 3.0, where R₂ is as originallydefined, using an aqueous acid solution such as hydrochloric acid (HCl)in a solvent such as ethanol (EtOH) at an elevated temperature, such as80° C., as shown in a. Compounds of Formula 3.2, where R₁ is TIPS and R₂is as originally defined, can be obtained from compounds of Formula 3.1,where R₂ is as defined above, by exposure to triisopropylsilyltrifluoro-methanesulfonate and an amine base, such as4-N,N-dimethylamino pyridine (DMAP), in a solvent such as DCM, as shownin b. Compounds of Formula 3.3, where R₁ is TIPS and R₂ is as originallydefined, can be prepared from compounds of Formula 3.2, where R₁ and R₂are as defined above, by treatment with a reducing agent such asdiisobutylaluminum hydride (DIBAl-H) in a solvent such as DCM, as shownin c. Compounds of Formula 3.4, where R₁ is TIPS and R₂ is as originallydefined and X is Boc or Cbz, can be prepared from compounds of Formula3.3, where R₁ and R₂ are as defined above, by treatment with a protectedaziridine of Formula 2.3, wherein X is Boc or Cbz, such as(S)-1-tert-butyl 2-methyl aziridine-1,2-dicarboxylate, in the presenceof a Lewis acid such as BF₃-Et₂O, in an aprotic solvent such as DCM, asshown in d. Compounds of Formula 3.5, where R₁, R₂, and X are as definedabove, can be prepared from compounds of Formula 3.4, where R₁, R₂, andX are as defined above and the carboxylic acid is protected as eitherthe methyl (Me) or benzyl (Bn) ester, by treating with a hydroxide base,such as LiOH, in an aqueous THF solvent mixture, as shown in e.Additionally, compounds of Formula 3.5, where R₁ and R₂ are as definedabove and X is Boc, can be prepared from compounds of Formula 3.4, whereR₁ and R₂ are as defined above, X is Boc, and the carboxylic acid isprotected as the benzyl (Bn) ester by treatment with hydrogen in thepresence of a catalyst such as Pd/C, in a solvent such as EtOAc, asshown in f.

Compounds of Formula 4.1, where R₁ is TIPS, alkyl, or an allylicfunctionality and R₂ is as originally defined and X is Boc or Cbz, canbe prepared according to the methods outlined in Scheme 4. Compounds ofFormula 4.1, can be obtained from compounds of Formula 4.0, where R₁ isTIPS, alkyl, or an allylic functionality and R₂ is as originally definedand X is Boc or Cbz, by the addition of a solution of compounds ofFormula 4.0 in a halogenated solvent such as DCM or an aromatic solventsuch as toluene to a mixture of a base, such as DMAP, and a mixedanhydride, such as 2-methyl-6-nitrobenzoic anhydride (MNBA), in either ahalogenated solvent such as DCM or an aromatic solvent such as tolueneover a period of 4-12 hours, as shown in a.

Compounds of formulas 5.1 and 5.2 can be prepared through the methodsshown in Scheme 5, steps a-b. Compounds of Formula 5.1, where R₁ is anallylic or alkyl functionality, R₂ is as originally defined, and X and Yare hydrogen, can be obtained from compounds of Formula 5.0, where R₁ isan allylic or alkyl functionality, R₂ is as originally defined, X isBoc, and Y is hydrogen, by treating with an acid, such as a 4.0 Mhydrogen chloride (HCl) solution in dioxane, in a solvent such as DCM,as shown in a. The resulting hydrochloride salt may be neutralized priorto use to give the free amine or neutralized in situ in step b.Compounds of Formula 5.2, where R₁ is an allylic or alkyl functionalityand R₂ is as originally defined, can be prepared from compounds ofFormula 5.1 by treatment with 3-hydroxy-4-methoxypicolinic acid in thepresence of a base, such as 4-methylmorpholine, and a peptide couplingreagent, such as O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HATU) orbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBOP), in an aprotic solvent such as DCM, as shown in b.

Compounds of Formulas 6.1-6.8 can be prepared as described in Scheme 6,steps a-h. Compounds of Formula 6.1, where R₁ is a trialkyl silyl grouplike TIPS, R₂ is as originally defined, and X and Y are Boc, can beprepared from compounds of Formula 6.0, where R₁ is a trialkyl silylgroup like TIPS, R₂ is as originally defined, X is Boc, and Y is H, bytreatment with a dicarbonate, such as di-tert-butyl dicarbonate (Boc₂O)in the presence of an amine base, such as DMAP, in a polar aproticsolvent such as acetonitrile (CH₃CN), as shown in a. Secondary alcoholsof Formula 6.2, where R₁ is H, R₂ is as originally defined, and X and Yare Boc, can be prepared by treating compounds of Formula 6.1, where R₁,R₂, X, and Y are as defined above, with a fluoride source, such astetrabutylammonium fluoride (TBAF), in an aprotic solvent such as THF,as shown in b. Compounds of Formula 6.3, where R₁ possesses an allylicfunctionality, R₂ is as originally defined, and X and Y are Boc, can beprepared from compounds of Formula 6.2, where R₁, R₂, X, and Y are asdefined above, by treating with an allyl carbonante, such astert-butyl(cyclopent-2-en-1-yl)carbonate, in the presence of a palladiumcatalyst with or without the addition of a phosphine ligand, such astetrakis(triphenylphosphine)palladium(0) (Pd(PPh₃)₄), or (Pd₂(dba)₃),and dppf, in an aprotic solvent such as toluene or THF, at elevatedtemperatures, such as 60-95° C., as shown in c. Compounds of Formula6.4, where R₁ is alkyl, R₂ is as originally defined, and X and Y areBoc, can be prepared from compounds of Formula 6.3, where R₁, R₂, X, andY are as defined above, by treating with hydrogen in the presences of acatalyst such as Pd/C or PtO₂ (platinum (IV) oxide), in a solvent suchas EtOAc, as shown in f. Compounds of Formula 6.5, where R₁ is acyl, R₂is as originally defined, and X and Y are Boc, can be prepared fromcompounds of Formula 6.2, where R₁, R₂, X, and Y are as defined above,by treating with a carbonyl chloride such as isobutyryl chloride in thepresence of an amine base such as DMAP, in a solvent such as DCM, asshown in d. Compounds of Formula 6.6, where R₁ is aryl, R₂ is asoriginally defined, and X and Y are Boc, can be prepared from compoundsof Formula 6.2, where R₁, R₂, X, and Y are as defined above, by treatingwith a triarylbismuth reagent, such as tritoluylbismuth diacetate, inthe presence of a copper catalyst, such as diacetoxycopper, and an aminebase, such as N,N-dicyclohexyl-methylamine, in an aprotic solvent suchas toluene at an elevated temperature of about 50° C., as shown in e.Compounds of Formula 6.7, where R₁ and R₂ are as originally defined, andX and Y are H, can be prepared from a variety of precursors, including,but not limited to, compounds of Formulas 6.3, 6.4, 6.5, and 6.6,wherein R₁, R₂, X, and Y have been previously defined above, by treatingwith an acid, such as a 4.0 M HCl solution in dioxane, in a solvent suchas DCM, as shown in g. The resulting hydrochloride salt may beneutralized prior to use to give the free amine or neutralized in situin step h. Compounds of Formula 6.8, where R₁ and R₂ are as originallydefined, can be prepared from compounds of Formula 6.7, where R₁, R₂, X,and Y are H, by treating with 3-hydroxy-4-methoxypicolinic acid in thepresence of a base, such as N-ethyl-N-isopropylpropan-2-amine, and apeptide coupling reagent, such as HATU or PyBOP, in an aprotic solventsuch as DCM, as shown in h.

Compounds of Formulas 7.3 and 7.4 can be prepared through the methodsshown in Scheme 7, steps a-d. Compounds of Formula 7.3, where R₁ and R₂are as originally defined and X and Y are H, can be prepared from avariety or precursors, including, but not limited to, compounds ofFormulas 7.0, 7.1, and 7.2, where R₁ and R₂ are as originally defined,and X is Boc (7.0), X and Y are Boc (7.1), and X is CBz (7.2),respectively. Treating compounds of Formulas 7.0 and 7.1 with an acid,such as a 4.0 M HCl solution in dioxane, in a solvent such as DCMaffords the hydrochloride salt of compounds of Formula 7.3, which may beneutralized in situ in step d or neutralized prior to use to give thefree amine, as shown in a. Additionally, compounds of Formula 7.3, whereR₁ and R₂ are as originally defined, can be prepared from compounds ofFormulas 7.0 and 7.1, where R₁, R₂, are as originally defined and X andY are Boc or Cbz, by treatment with trimethylsilyltrifluoromethanesulfonate in the presence of a base, such as2,6-lutidine, in an aprotic solvent such as DCM, followed by treatmentwith a protic solvent such as MeOH, as shown in b. Alternatively,compounds of Formula 7.3, where R₁ and R₂ are as originally defined andX and Y are H, can be prepared from compounds of Formula 7.2, where R₁and R₂ are as originally defined and X is CBz, by treatment withhydrogen in the presence of a catalyst, such as Pd/C, in a solvent suchas EtOAc, as shown in c. Compounds of Formula 7.4, where R₁ and R₂ areas originally defined, can be prepared from compounds of Formula 7.3,where R₁ and R₂ are as defined above, by treatment with3-hydroxy-4-methoxypicolinic acid in the presence of a base, such as4-methylmorpholine, and a peptide coupling reagent, such as HATU orPyBOP, in an aprotic solvent such as DCM, as shown in step d.

Compounds of Formula 8.1, where R₁, R₂ and R₄ are as originally defined,can be prepared by the method shown in Scheme 8. Compounds of Formula8.1 can be prepared from compounds of Formula 8.0, where R₁ and R₂ areas originally defined, by treatment with the appropriate alkyl halidewith or without a reagent such as sodium iodide (NaI) and an alkalicarbonate base such as sodium carbonate (Na₂CO₃) or potassium carbonate(K₂CO₃) in a solvent such as acetone or by treatment with an acyl halidein the presence of an amine base, such as pyridine, triethylamine, DMAP,or mixtures thereof in an aprotic solvent such as DCM, as shown in a.

The following examples are presented to illustrate the various aspectsof the compounds of the present disclosure and should not be construedas limitations to the claims.

EXAMPLES Example 1 Step 1: Preparation of(R)-4-benzyl-3-(3-(p-tolyl)propanoyl)-oxazolidin-2-one

To a solution of 3-(p-tolyl)propanoic acid (8.0 grams (g), 48.7millimoles (mmol)) in dichloroethane (DCE, 100 milliliters (mL)) wasadded oxalyl chloride (30.9 g, 20.6 mL, 243 mmol) followed by 1 drop ofDMF, and the resulting gold colored mixture was stirred at roomtemperature. Within 90 minutes (min) all of the solids had dissolved andgas evolution had subsided. The solution was stirred for an additional 2hours (h) and then the solvent and excess oxalyl chloride wereevaporated on the rotary evaporator. The resulting yellow oil wasdissolved in anhydrous THF (25 mL) and the solvent was evaporated(repeated 2×). The residual yellow oil was dissolved in anhydrous THF (5mL) and used immediately in the next step.

To a solution of (R)-4-benzyloxazolidin-2-one (7.5 g, 42.3 mmol) inanhydrous THF (140 mL) was added n-BuLi (17.8 mL of 2.5 M in hexanes,44.4 mmol) dropwise at −78° C. over a 20 min period. The solution wasclear to light yellow during most of the addition and then graduallyturns orange upon completion. The resulting orange solution was stirredat −78° C. for 45 min and was then treated dropwise with the propanoylchloride prepared above at −75 to −78° C. The resulting light brownsolution was stirred at −78° C. for 2 h, slowly warmed to roomtemperature, and stirred for 16 h at room temperature. The homogeneousbrown solution was neutralized with saturated aqueous ammonium chloride(NH₄Cl, 100 mL), and the majority of the THF was removed on the rotaryevaporator. The aqueous residue was extracted with CH₂Cl₂ (3×100 mL),and the combined organic extracts were washed with brine (100 mL), driedover sodium sulfate (Na₂SO₄), filtered, and concentrated to a tan solid.The solid was recrystallized from 25% ethyl acetate (EtOAc) in hexanes(150 mL), and the resulting crystals were collected by vacuumfiltration, washed with ice cold 20% EtOAc in hexanes, and dried undervacuum to give (R)-4-benzyl-3-(3-(p-tolyl)propanoyl)oxazolidin-2-one(10.57 g, 77%) as pale yellow needles: mp 124-126° C.; ¹H NMR (400 MHz,CDCl₃) δ 7.29 (m, 3H), 7.17 (m, 4H), 7.11 (m, 2H), 4.65 (m, 1H), 4.16(m, 2H), 3.26 (m, 3H), 2.99 (m, 2H), 2.75 (m, 1H), 2.32 (s, 3H); ESIMSm/z 346 ([M+Na]⁺).

Example 1 Step 2: Preparation of(R)-4-benzyl-3-((2R,3R,4S)-4-(benzyloxy)-3-hydroxy-2-(4-methylbenzyl)pentanoyl)oxazolidin-2-one

To a solution of (R)-4-benzyl-3-(3-(p-tolyl)propanoyl)oxazolidin-2-one(2.5 g, 7.73 mmol) in CH₂Cl₂ (30 mL) was addeddibutyl(((trifluoromethyl)sulfonyl)oxy)borane (8.5 mL of 1M in CH₂Cl₂,8.5 mmol) dropwise at 0° C., and the resulting brown solution wasstirred for 10 min. Triethylamine (TEA, 1.1 g, 10.82 mmol) was addeddropwise, and the resulting light yellow solution was stirred for 1 h,and then cooled to −78° C. A solution of (S)-2-(benzyloxy)propanal (1.65g, 10.05 mmol), prepared according to the method described in Enders,D., von Berg, S., Jandeleit, B. Organic Synthesis 2002, 78, 177, inCH₂Cl₂ (3 mL) was added dropwise and the reaction was stirred at −78° C.for 1 h. The dry ice/acetone bath was replaced with an ice/acetone bathand the reaction was stirred at −10° C. for 1 h. The reaction wasquenched with a 2:1 solution of MeOH/pH=7 phosphate buffer (24 mL total)followed by a 2:1 solution of MeOH/30% hydrogen peroxide (H₂O₂; 6 mLtotal, 2 mL peroxide, −20 mmol), and then stirred at 0° C. for 1 h. Thephases were separated and the aqueous phase was extracted withadditional CH₂Cl₂ (2×50 mL). The combined organic phases were washedwith aqueous sodium bicarbonate (NaHCO₃), washed with brine, dried overmagnesium sulfate (MgSO₄), filtered, and concentrated to give 4.6 g of alight yellow oil. Purification by flash chromatography (silica gel(SiO₂), 0→40% EtOAc/hexanes) afforded(R)-4-benzyl-3-((2R,3R,4S)-4-(benzyloxy)-3-hydroxy-2-(4-methylbenzyl)pentanoyl)-oxazolidin-2-one(3.18 g, 84%) as a colorless, sticky glass: ¹H NMR (400 MHz, CDCl₃) δ7.26 (m, 10H), 7.04 (d, J=7.8 Hz, 2H), 6.92 (dd, J=7.6, 1.6 Hz, 2H),4.74 (m, 1H), 4.63 (d, J=11.6 Hz, 1H), 4.31 (d, J=11.6 Hz, 1H), 4.23(ddt, J=8.1, 6.6, 3.3 Hz, 1H), 3.97 (td, J=6.8, 4.9 Hz, 1H), 3.68 (dd,J=9.0, 3.1 Hz, 1H), 3.55 (m, 1H), 3.38 (t, J=8.4 Hz, 1H), 3.24 (dd,J=13.4, 5.4 Hz, 1H), 2.95 (dd, J=13.4, 10.4 Hz, 1H), 2.80 (dd, J=13.6,3.4 Hz, 1H), 2.59 (d, J=4.9 Hz, 1H), 2.27 (s, 3H), 1.81 (dd, J=13.6,10.3 Hz, 1H), 1.34 (d, J=6.1 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 175.08,152.94, 138.43, 135.87, 135.57, 135.18, 129.54, 129.09, 128.91, 128.79,128.27, 127.48, 127.33, 127.03, 76.78, 75.35, 70.27, 65.30, 54.66,46.15, 37.20, 34.73, 21.00, 15.88; ESIMS m/z 511 ([M+Na]⁺).

Example 2 Step 1: Preparation of(R)-4-benzyl-3-((2R,3R,4S)-4-(benzyloxy)-3-((2-methylallyl)oxy)-2-(4-methylbenzyl)pentanoyl)oxazolidin-2-one

To a 250 mL round bottom flask were added(R)-4-benzyl-3-((2R,3R,4S)-4-(benzyloxy)-3-hydroxy-2-(4-methylbenzyl)pentanoyl)oxazolidin-2-one(11.2 g, 23 mmol) and anhydrous THF (145 mL). The solution was spargedwith N₂ for 5 min and then tris(dibenzylideneacetone)-dipalladium (0)(Pd₂(dba)₃; 2.10 g, 2.3 mmol) and 1,1′-bis(diphenylphosphino)ferrocene(dppf; 2.55 g, 4.59 mmol) were added, and the resulting dark solutionwas sparged with N₂ for an additional 5 minutes. The reaction mixturewas warmed to 55° C. under N₂ and treated with a solution oftert-butyl(2-methylallyl) carbonate (7.9 g, 45.9 mmol) in THF (5 mL).The dark mixture was stirred at 55° C. for 1 h and then cooled to roomtemperature, The reaction mixture was filtered through paper, rinsingwith CH₂Cl₂, and the filtrate was evaporated to give a dark oil. The oilwas partially purified by flash chromatography (SiO₂, 0→30%acetone/hexanes) to give(R)-4-benzyl-3-((2R,3R,4S)-4-(benzyloxy)-3-((2-methylallyl)oxy)-2-(4-methylbenzyl)pentanoyl)oxazolidin-2-one(9.36 g) as a yellow oil that is contaminated with dibenzylideneacetone(dba): ¹H NMR (400 MHz, CDCl₃) δ 7.22 (m, 10H), 7.02 (d, J=7.8 Hz, 2H),6.87 (m, 2H), 5.06 (m, 1H), 4.91 (s, 1H), 4.77 (ddd, J=11.7, 9.3, 4.7Hz, 1H), 4.64 (d, J=11.9 Hz, 1H), 4.31 (d, J=11.9 Hz, 1H), 4.16 (s, 2H),3.96 (m, 1H), 3.74 (dd, J=9.2, 7.1 Hz, 1H), 3.62 (p, J=6.1 Hz, 1H), 3.41(m, 2H), 2.85 (m, 2H), 2.70 (dd, J=13.7, 3.5 Hz, 1H), 2.26 (s, 3H), 2.17(s, 3H), 1.49 (dd, J=13.7, 10.6 Hz, 1H), 1.34 (d, J=6.1 Hz, 3H); ESIMSm/z 565 ([M+Na]⁺).

Example 2 Step 2: Preparation of(2S,3R,4S)-4-(benzyloxy)-3-((2-methylallyl)-oxy)-2-(4-methylbenzyl)pentan-1-ol

To a solution of(R)-4-benzyl-3-((2R,3R,4S)-4-(benzyloxy)-3-((2-methylallyl)oxy)-2-(4-methylbenzyl)pentanoyl)oxazolidin-2-one(9.36 g, 17.3 mmol) in aqueous THF (4:1 THF/H₂O; 86 mL) was addedlithium borohydride (34.6 mL of 2.0 M in THF, 69.1 mmol) dropwise at −5°C., and the resulting yellow solution was vigorously stirred. After 1 hthe yellow color (dba) had dissipated and the reaction was allowed toslowly warm to room temperature. The reaction was stirred for anadditional 5 h and then poured into ice cold saturated aqueous NH₄Cl(250 mL). The phases were separated and the aqueous was extracted withCH₂Cl₂ (3×100 mL). The combined organics phases were dried over Na₂SO₄,filtered, and concentrated to a light yellow oil (10.11 g), which waspurified by both reverse phase (RP; Cl 8, 0→100% CH₃CN/H₂O) and normalphase (NP: SiO₂, 0→30% EtOAc/CH₂Cl₂) to give(2S,3R,4S)-4-(benzyloxy)-3-((2-methylallyl)oxy)-2-(4-methylbenzyl)pentan-1-ol(4.04 g, 48% from Ex. 2, Step 1) as a colorless liquid: ¹H NMR (400 MHz,CDCl₃) δ 7.32 (m, 5H), 7.06 (m, 4H), 4.98 (m, 1H), 4.87 (m, 1H), 4.64(d, J=11.6 Hz, 1H), 4.44 (d, J=11.6 Hz, 1H), 4.08 (d, J=11.6 Hz, 1H),3.97 (d, J=12.1 Hz, 1H), 3.78 (p, J=6.2 Hz, 1H), 3.56 (m, 3H), 2.88 (dd,J=13.8, 4.7 Hz, 1H), 2.53 (dd, J=13.8, 10.1 Hz, 1H), 2.30 (s, 3H), 2.18(ddd, J=14.4, 7.7, 4.3 Hz, 1H), 2.01 (dd, J=6.2, 4.9 Hz, 1H), 1.76 (s,3H), 1.33 (d, J=6.2 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 142.41, 138.50,137.87, 135.28, 129.00, 128.37, 127.75, 127.57, 111.86, 83.08, 75.92,75.73, 70.79, 62.83, 44.60, 32.63, 21.05, 20.99, 19.84, 16.33; ESIMS m/z391 ([M+Na]⁺).

Example 2 Step 3: Preparation of (S)-methyl3-((2S,3R,4S)-4-(benzyloxy)-3-((2-methylallyl)oxy)-2-(4-methylbenzyl)pentyl)oxy)-2-((tert-butoxycarbonyl)amino)propanoate

To a solution of(2S,3R,4S)-4-(benzyloxy)-3-((2-methylallyl)oxy)-2-(4-methylbenzyl)pentan-1-ol(0.51 g, 1.38 mmol) and (diethyloxonio)trifluoroborate (BF₃(OEt)₂), 0.02g, 0.14 mmol) in CH₂Cl₂ (9 mL) was added a solution of (S)-1-tert-butyl2-methylaziridine-1,2-dicarboxylate (0.40 g, 1.99 mmol) in CH₂Cl₂ (4.0mL) slowly (syringe pump: 1.0 mL/h) at room temperature. After 3 h, thereaction mixture was treated with 2 μL of BF₃(OEt)₂, while the aziridineaddition was continued., and at the 4 and 5 h time points HPLC-MSindicated 74 and 84% conversion to desired product. An additional 2 μLof BF₃(OEt)₂ were added and the reaction mixture was stirred for 1 h andthen treated with a final 2 μL dose of BF₃(OEt)₂ and 0.1 equivalents ofthe aziridine. After 1 h of stirring, the reaction mixture was adsorbedto Celite® (3.3 g) and purified by flash chromatography (SiO₂, 0→20%acetone/hexanes) to give (S)-methyl3-((2S,3R,4S)-4-(benzyloxy)-3-((2-methylallyl)oxy)-2-(4-methylbenzyl)pentyl)oxy)-2-((tert-butoxycarbonyl)amino)propanoate(0.46 g, 58%) as a colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 7.32 (m,5H), 7.05 (d, J=7.8 Hz, 2H), 6.98 (d, J=8.0 Hz, 2H), 5.30 (d, J=9.0 Hz,1H), 5.00 (m, 1H), 4.87 (m, 1H), 4.61 (d, J=11.7 Hz, 1H), 4.44 (d,J=11.7 Hz, 1H), 4.39 (m, 1H), 4.09 (d, J=12.0 Hz, 1H), 3.88 (d, J=12.0Hz, 1H), 3.72 (s, 3H), 3.68 (m, 2H), 3.49 (dt, J=8.8, 4.3 Hz, 2H), 3.23(m, 2H), 2.92 (dd, J=13.7, 3.9 Hz, 1H), 2.38 (dd, J=13.7, 10.7 Hz, 1H),2.31 (s, 3H), 2.21 (dq, J=6.9, 3.7 Hz, 1H), 1.78 (s, 3H), 1.43 (s, 9H),1.27 (d, J=6.2 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 171.14, 155.49,142.79, 138.73, 137.86, 135.23, 128.94, 128.33, 127.68, 127.47, 111.54,81.57, 79.98, 77.22, 76.34, 75.57, 70.78, 70.66, 70.52, 53.94, 52.35,42.09, 32.26, 28.31, 21.00, 19.89, 16.01; ESIMS m/z 594 ([M+Na+H]⁺).

Example 2 Step 4: Preparation of (S)-methyl2-((tert-butoxycarbonyl)amino)-3-(((2S,3R,4S)-4-hydroxy-3-isobutoxy-2-(4-methylbenzyl)pentyl)oxy)propanoate

To a solution of (S)-methyl3-((2S,3R,4S)-4-(benzyloxy)-3-((2-methylallyl)oxy)-2-(4-methylbenzyl)pentyl)oxy)-2-((tert-butoxycarbonyl)amino)propanoate(3.0 g, 5.27 mmol) in ethyl alcohol (EtOH; 21 mL) was added Pd/C (10%,˜200 mg), and the mixture was sparged with N₂. The reaction flask wasevacuated and backfilled with N₂ three times, evacuated and backfilledwith H₂ three times, and then stirred under 1 atmosphere (atm) of H₂ for16 h. The reaction mixture was treated with additional catalyst (0.2 g)and resubjected to the hydrogenation/hydrogenolysis conditions asdescribed above for an additional 5 h. The reaction flask was evacuatedand backfilled with N₂ (4×) and then the reaction mixture was spargedwith N₂ for 10 min. The mixture was filtered through Celite®, rinsingwith EtOH, and the filtrate was passed through a 2 μm syringe filter,and then concentrated to a colorless oil. The oil was purified by flashchromatography (SiO₂, 0→30% acetone/hexanes) to give (S)-methyl2-((tert-butoxycarbonyl)amino)-3-((2S,3R,4S)-4-hydroxy-3-isobutoxy-2-(4-methylbenzyl)pentyl)-oxy)propanoate(2.099 g, 83%) as a colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 7.05 (m,4H), 5.36 (d, J=8.7 Hz, 1H), 4.43 (dd, J=5.4, 3.3 Hz, 1H), 3.90 (m, 1H),3.76 (s, 3H), 3.72 (m, 1H), 3.56 (dd, J=9.3, 3.0 Hz, 1H), 3.24 (m, 5H),2.94 (dd, J=13.8, 4.4 Hz, 1H), 2.47 (dd, J=13.7, 10.8 Hz, 1H), 2.32 (s,3H), 2.12 (dq, J=6.7, 3.4 Hz, 1H), 1.84 (dq, J=13.2, 6.6 Hz, 1H), 1.45(s, 9H), 1.26 (d, J=6.3 Hz, 4H), 0.93 (dd, J=6.7, 2.7 Hz, 6H); ¹³C NMR(101 MHz, CDCl₃) δ 171.06, 155.40, 137.83, 135.36, 129.04, 128.87,83.26, 80.07, 78.59, 71.11, 70.00, 68.47, 53.94, 52.47, 42.56, 34.67,33.20, 31.60, 29.09, 28.32, 22.66, 21.01, 19.57, 19.52, 19.49; ESIMS m/z505 ([M+Na]⁺).

Example 2 Step 5: Preparation of(S)-2-((tert-butoxycarbonyl)amino)-3-(((2S,3R,4S)-4-hydroxy-3-isobutoxy-2-(4-methylbenzyl)pentyl)oxy)propanoicacid

To a solution of (S)-methyl2-((tert-butoxycarbonyl)amino)-3-(((2S,3R,4S)-4-hydroxy-3-isobutoxy-2-(4-methylbenzyl)pentyl)oxy)propanoate(2.06 g, 4.28 mmol) in aqueous THF (16 THF:5 H₂O; 21 mL total volume)was added LiOH—H₂O (0.54 g, 12.83 mmol) and the reaction was stirred for4 h at room temperature. The reaction was diluted with H₂O (50 mL) andthe majority of the THF was removed on the rotovap. The aqueous residuewas acidified with 2 N HCl and extracted with CH₂Cl₂ (6×50 mL) until theaqueous phase was nearly clear. The combined organic extracts werewashed with brine (2×50 mL), dried over Na₂SO₄, filtered, andconcentrated to a colorless oil (1.96 g). The oil was purified by RPflash chromatography (C18; 0→85% CH₃CN/H₂O) to give(S)-2-((tert-butoxycarbonyl)amino)-3-(((2S,3R,4S)-4-hydroxy-3-isobutoxy-2-(4-methyl-benzyl)pentyl)oxy)-propanoicacid (1.71 g, 85%) as a colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 7.05(m, 4H), 6.57 (s, 2H), 5.47 (d, J=8.1 Hz, 1H), 4.44 (m, 1H), 3.92 (m,1H), 3.77 (m, 1H), 3.58 (m, 1H), 3.41 (d, J=7.2 Hz, 1H), 3.24 (m, 4H),2.91 (dd, J=13.7, 4.0 Hz, 1H), 2.46 (dd, J=13.7, 10.8 Hz, 1H), 2.31 (s,3H), 2.10 (dd, J=6.8, 3.3 Hz, 1H), 1.81 (dp, J=13.2, 6.6 Hz, 1H), 1.44(s, 9H), 1.25 (d, J=6.2 Hz, 3H), 0.91 (dd, J=6.7, 2.7 Hz, 6H); ¹³C NMR(101 MHz, CDCl₃) δ 171.72, 153.71, 135.81, 133.44, 127.15, 127.02,81.61, 78.33, 76.81, 69.13, 68.31, 67.08, 51.93, 40.98, 31.48, 27.16,26.42, 19.12, 17.65, 17.58, 17.38; ESIMS m/z 491 ([M+Na]⁺).

Example 3 Step 1: Preparation of(3R,4R,5S)-4-hydroxy-5-methyl-3-phenethyldihydro-furan-2(3H)-one and(R)-4-benzyloxazolidin-2-one

To a solution of(R)-4-benzyl-3-((2R,3R,4S)-3-hydroxy-2-phenethyl-4-((triisopropylsilyl)oxy)pentanoyl)-oxazolidin-2-one(2.52 g, 4.55 mmol) in EtOH (18 mL) was added 1 N HCl (2 mL, 2 mmol) andthe mixture heated to 80° C. for a 3 h. The solution was concentrated invacuo, and the residue was dissolved in CH₂Cl₂, loaded onto a pre-packedCelite° cartridge, and purified by flash chromatography (SiO₂, 0→100%EtOAc/hexanes) gave(3R,4R,5S)-4-hydroxy-5-methyl-3-phenethyldihydrofuran-2(3H)-one (840 mg,3.81 mmol, 84% yield) and (R)-4-benzyloxazolidin-2-one (710 mg, 4.01mmol, 88% yield). The title product was obtained as a colorless,amorphous solid: ¹H NMR (600 MHz, CDCl₃) δ 7.33-7.28 (m, 2H), 7.25-7.19(m, 3H), 4.20-4.13 (m, 1H), 3.80 (dd, J=8.9, 7.3 Hz, 1H), 2.96-2.88 (m,1H), 2.86-2.79 (m, 1H), 2.59-2.52 (m, 1H), 2.28-2.17 (m, 2H), 1.97-1.88(m, 1H), 1.43 (d, J=6.3 Hz, 3H); ¹³C NMR (151 MHz, CDCl₃) δ 175.91,140.94, 128.64, 128.51, 126.34, 79.89, 79.36, 47.98, 32.81, 30.25,18.19; ESIMS m/z 221 ([M+H]⁺).

Example 3 Step 2: Preparation of(3R,4R,5S)-5-methyl-3-phenethyl-4-((triisopropylsilyl)oxy)dihydrofuran-2(3H)-one

To a solution of(3R,4R,5S)-4-hydroxy-5-methyl-3-phenethyldihydrofuran-2(3H)-one (800 mg,3.63 mmol) in CH₂Cl₂ (20 mL) were added 2,6-dimethylpyridine (592 μl,5.08 mmol) and triisopropylsilyl trifluoromethanesulfonate (1171 μl,4.36 mmol) at 0° C., and the mixture was warmed to room temperaturewhile stirring overnight. The reaction mixture was poured onto 50 mLsaturated sodium bicarbonate solution and mixed thoroughly. The phaseswere separated, and the aqueous extracted with CH₂Cl₂ (2×25 mL). Thecombined CH₂Cl₂ extracts were dried and concentrated to a colorless oilwhich was purified by flash chromatography (SiO₂, 0→50% EtOAc/hexanes)to give(3R,4R,5S)-5-methyl-3-phenethyl-4-((triisopropylsilyl)oxy)dihydro-furan-2(3H)-one(809 mg, 53%): ¹H NMR (400 MHz, CDCl₃) δ 7.33-7.25 (m, 2H), 7.25-7.17(m, 3H), 3.98 (dd, J=5.9, 4.8 Hz, 1H), 4.34-4.24 (m, 1H), 2.99-2.88 (m,1H), 2.88-2.76 (m, 1H), 2.61-2.51 (m, 1H), 2.04-1.94 (m, 2H), 1.43 (d,J=6.5 Hz, 3H), 1.09-0.99 (m, 21H); ¹³C NMR (101 MHz, CDCl₃) δ 176.64,140.98, 128.57, 128.51, 126.16, 82.10, 79.45, 49.17, 32.96, 31.14,19.10, 18.00, 17.71; ESIMS m/z 378 ([M+H]⁺).

Example 3 Step 3: Preparation of(2S,3R,4S)-2-phenethyl-3-((triisopropylsilyl)-oxy)pentane-1,4-diol

To an oven-dried flask were added(3R,4R,5S)-5-methyl-3-phenethyl-4-((triisopropyl-silyl)oxy)dihydrofuran-2(3H)-one(670 mg, 1.601 mmol) and CH₂Cl₂ (8 mL)) and the mixture was cooled to−78° C. and treated with DIBAL-H (1.0 M in CH₂Cl₂, 4.00 mL, 4.00 mmol)dropwise over 10 min. The dry ice/acetone bath was removed and themixture allowed to warm to room temperature while stirring overnight.The reaction was cooled to 0° C. and quenched by addition of saturatedpotassium sodium tartrate solution (50 mL). The mixture was diluted withCH₂Cl₂ (25 mL) and stirred until two clean-splitting phases were formed.The phases were separated, and the aqueous extracted further withCH₂Cl₂. The combined organic extracts were dried and concentrated to acolorless oil which was purified by flash chromatography (SiO₂, 0→30%EtOAc/hexanes) to give(2S,3R,4S)-2-phenethyl-3-((triisopropylsilyl)oxy)pentane-1,4-diol (422mg, 69%): ¹H NMR (400 MHz, CDCl₃) δ 7.30-7.23 (m, 2H), 7.21-7.14 (m,3H), 4.02-3.92 (m, 2H), 3.77 (dd, J=4.3, 3.1 Hz, 1H), 3.72-3.61 (m, 1H),3.18 (s, 1H), 2.92-2.76 (m, 2H), 2.62-2.51 (m, 1H), 2.10-1.96 (m, 1H),1.80-1.62 (m, 2H), 1.27 (d, J=6.7 Hz, 3H), 1.07-0.93 (m, 21H); ¹³C NMR(101 MHz, CDCl₃) δ 141.94, 128.48, 128.36, 125.86, 78.18, 71.24, 59.48,45.39, 34.24, 29.69, 18.64, 18.14, 18.10, 12.54; ESIMS m/z 403([M+Na]⁺).

Example 4 Step 1: Preparation oftert-butyl((3S,7S,8R,9S)-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-2-oxo-1,5-dioxonan-3-yl)carbamate(F170)

To a magnetically stirred solution of DMAP (3.22 g, 26.3 mmol) and MNBA(2.07 g, 6.02 mmol) in anhydrous toluene (750 mL) was added a solutionof(S)-2-((tert-butoxycarbonyl)amino)-3-(((2S,3R,4S)-4-hydroxy-3-isobutoxy-2-(4-methylbenzyl)pentyl)oxy)-propanoicacid (1.76 g, 3.76 mmol) in anhydrous toluene (60 mL) dropwise over 5.5h (syringe pump), and the resulting turbid mixture was stirred for 16 h.The reaction mixture was filtered through paper and the filtrate wasconcentrated to a pale yellow solid which was purified by flashchromatography (SiO₂, 0→30% acetone/hexanes) to givetert-butyl((3S,7S,8R,9S)-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-2-oxo-1,5-dioxonan-3-yl)carbamate(1.48 g, 87%) as a white foam: ¹H NMR (400 MHz, CDCl₃) δ 7.09 (d, J=8.2Hz, 2H), 7.06 (d, J=8.2 Hz, 2H), 5.14 (d, J=8.2 Hz, 1H), 4.95 (dq,J=9.2, 6.4 Hz, 1H), 4.59 (q, J=7.3 Hz, 1H), 3.87 (dd, J=11.5, 7.3 Hz,1H), 3.44 (t, J=7.4 Hz, 2H), 3.32 (tdd, J=16.8, 10.6, 5.2 Hz, 3H), 3.10(dd, J=10.4, 6.6 Hz, 2H), 2.31 (s, 3H), 2.24 (t, J=12.7 Hz, 1H), 1.88(dq, J=13.2, 6.6 Hz, 2H), 1.47 (d, J=6.4 Hz, 3H), 1.41 (s, 9H), 0.95 (d,J=6.7 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ 172.24, 154.95, 136.81,135.52, 129.10, 129.01, 84.66, 80.02, 79.21, 75.57, 72.86, 72.48, 52.97,47.40, 34.56, 29.17, 28.27, 21.01, 19.48, 18.80; ESIMS m/z 473([M+Na]⁺).

Example 4 Step 2: Preparation of tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-9-methyl-7-(1-naphthylmethyl)-2-oxo-8-triisopropylsilyloxy-1,5-dioxonan-3-yl]carbamate

To a solution oftert-butyl((3S,7S,8R,9S)-9-methyl-7-(naphthalen-1-ylmethyl)-2-oxo-8-((triisopropylsilyl)oxy)-1,5-dioxonan-3-yl)carbamate(2.8 g, 4.78 mmol) and DMAP (0.292 g, 2.39 mmol) in CH₃CN (23.9 mL) wasadded di-tert-butyl dicarbonate (4.17 g, 19.1 mmol) at room temperatureand the reaction was stirred for 16 h at room temperature. The crudereaction mixture was adsorbed to Celite® and purified via flashchromatography (SiO₂, 0→20% EtOAc/hexanes) to give tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-9-methyl-7-(1-naphthylmethyl)-2-oxo-8-triisopropylsilyloxy-1,5-dioxonan-3-yl]carbamate(2.85 g, 87%) as a white foam: ¹H NMR (400 MHz, CDCl₃) δ 8.04-7.96 (m,1H), 7.87-7.80 (m, 1H), 7.71 (dd, J=8.2, 1.3 Hz, 1H), 7.52-7.36 (m, 4H),5.24 (app q, J=3.1 Hz, 1H), 5.06 (app t, J=7.9 Hz, 1H), 4.11 (dd, J=5.9,2.9 Hz, 1H), 4.08 (d, J=7.9 Hz, 2H), 3.75-3.63 (m, 2H), 3.37 (m, 2H),2.32-2.22 (m, 1H), 1.52 (d, J=7.0 Hz, 3H), 1.47 (s, 18H), 1.04 (m, 21H);¹³C NMR (101 MHz, CDCl₃) δ 169.53, 152.75, 136.39, 134.08, 131.92,128.95, 127.65, 126.82, 125.70, 125.45, 125.37, 123.68, 82.84, 78.92,76.93, 73.31, 71.12, 58.06, 48.83, 30.74, 27.91, 19.92, 18.17, 18.14,12.73; ESIMS m/z 709 ([M+Na]⁺).

Example 5 Steps 1a and 1b: Preparation of3-hydroxy-N-((3S,7S,8R,9S)-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-2-oxo-1,5-dioxonan-3-yl)-4-methoxypicolinamide(F48)

Step 1a

To a solution oftert-butyl((3S,7S,8R,9S)-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-2-oxo-1,5-dioxonan-3-yl)carbamate(0.03 g, 0.07 mmol) in CH₂Cl₂ (0.7 mL) was added a 4 M solution of HClin dioxane (0.33 mL, 1.34 mmol), and the resulting colorless solutionwas stirred at room temperature for 1.5 h. The solvent was evaporatedunder a positive stream of N₂ and the residue was dissolved in CH₂Cl₂,washed with saturated aqueous NaHCO₃, dried by passing through a phaseseparator cartridge, and concentrated to give(3S,7S,8R,9S)-3-amino-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-1,5-dioxonan-2-one(0.021 g, 90%) as a white solid: mp 81-84° C.; ¹H NMR (400 MHz, CDCl₃) δ7.08 (t, J=2.7 Hz, 4H), 4.91 (dq, J=9.2, 6.4 Hz, 1H), 3.84 (dd, J=11.6,7.5 Hz, 1H), 3.74 (m, 2H), 3.64 (m, 1H), 3.47 (dd, J=8.3, 6.4 Hz, 1H),3.41 (dd, J=10.7, 6.1 Hz, 1H), 3.31 (m, 2H), 3.07 (m, 3H), 2.31 (s, 3H),1.87 (m, 2H), 1.59 (m, 1H), 1.47 (d, J=6.4 Hz, 3H), 0.95 (dd, J=6.7, 1.6Hz, 6H); ESIMS m/z 351 ([M+H]⁺).

Step 1b

To a mixture of 3-hydroxy-4-methoxypicolinic acid (0.198 g, 1.17 mmol),HATU (0.47 g, 1.25 mmol), and N-methylmorpholine (0.47 g, 4.7 mmol) inCH₂Cl₂ (9 mL) was added(3S,7S,8R,9S)-3-amino-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-1,5-dioxonan-2-one(272 mg, 0.78 mmol), and the tan mixture was stirred at room temperaturefor 7 h. The resulting homogeneous solution was adsorbed to Celite® andpurified by flash chromatography (SiO₂, 0→30% acetone/hexanes) to give3-hydroxy-N-((3S,7S,8R,9S)-8-isobutoxy-9-methyl-7-(4-methylbenzyl)-2-oxo-1,5-dioxonan-3-yl)-4-methoxypicolinamide(0.30 g, 77%) as a white foam: ¹H NMR (400 MHz, CDCl₃) δ 11.95 (s, 1H),8.54 (d, J=8.3 Hz, 1H), 7.97 (d, J=5.2 Hz, 1H), 7.09 (d, J=2.1 Hz, 4H),6.85 (d, J=5.2 Hz, 1H), 5.01 (m, 2H), 4.02 (dd, J=11.7, 7.3 Hz, 1H),3.92 (s, 3H), 3.46 (m, 4H), 3.34 (dd, J=8.3, 6.5 Hz, 1H), 3.13 (m, 2H),2.31 (s, 4H), 1.93 (m, 2H), 1.50 (d, J=6.4 Hz, 3H), 0.96 (d, J=6.7 Hz,6H); ¹³C NMR (101 MHz, CDCl₃) δ 171.15, 168.90, 155.31, 148.71, 140.62,136.76, 135.58, 130.20, 129.15, 129.05, 109.56, 84.61, 79.28, 75.92,72.53, 72.16, 56.08, 51.53, 47.47, 34.60, 29.20, 21.03, 19.50, 18.83;HRMS-ESI (m/z) [M+H]⁺ calcd for C₂₇H₃₆N₂O₇, 500.2523. found, 500.2529.

Example 6 Step 1: Preparation of tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-hydroxy-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate

To a solution of tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-9-methyl-7-(1-naphthylmethyl)-2-oxo-8-triisopropylsilyloxy-1,5-dioxonan-3-yl]carbamate(2.54 g, 3.70 mmol) in THF (18.5 ml) was added TBAF (1.94 g, 7.41 mmol,1M in THF) at room temperature. The reaction was stirred for 3.5 h,diluted with a 1/2 sat. aqueous NaCl solution (10 mL), and extractedwith EtOAc (3×10 mL). The combined extracts were dried over Na₂SO₄,filtered, and concentrated to dryness under reduced pressure. Theresulting clear oil was purified by flash chromatography (SiO₂, 0→50%acetone/hexanes) to afford tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-hydroxy-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate(1.41 g, 72%) as a white solid: ¹H NMR (400 MHz, CDCl₃) δ 8.11 (dd,J=8.5, 1.4 Hz, 1H), 7.87-7.79 (m, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.54-7.41(m, 2H), 7.42-7.27 (m, 2H), 5.19 (dd, J=8.8, 5.7 Hz, 1H), 5.00-4.88 (m,1H), 4.10 (dd, J=11.9, 5.8 Hz, 1H), 3.89 (dd, J=12.0, 8.7 Hz, 1H),3.68-3.51 (m, 4H), 2.79 (t, J=12.2 Hz, 1H), 2.58-2.51 (m, 1H), 2.15 (q,J=8.7, 7.4 Hz, 1H), 1.51 (d, J=6.4 Hz, 3H), 1.46 (s, 18H); ¹³C NMR (101MHz, CDCl₃) δ 169.95, 152.69, 135.84, 134.02, 132.04, 128.77, 127.46,127.16, 126.03, 125.56, 125.25, 124.04, 83.17, 77.69, 76.26, 73.23,70.87, 57.38, 46.90, 33.38, 27.92, 18.67; ESIMS m/z 553 ([M+Na]⁺).

Example 6 Step 2a-1: Preparation of tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-cyclopent-2-en-1-yloxy-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate

To a solution of tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-hydroxy-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate(205 mg, 0.387 mmol), [Pd₂(dba)₃] (26.6 mg, 0.029 mmol), and dppf (32.5mg, 0.058 mmol) in toluene (1.94 mL) was added (E) tert-butylcyclopent-2-en-1-yl carbonate (250 mg, 1.355 mmol), and the mixture waswarmed to 95° C. and stirred for 2 h. An additional portion of(E)-tert-butyl pent-2-en-1-yl carbonate (150 mg, 0.6 equiv.) was addedto the reaction and stirring continued for an additional 2 h. Themixture was cooled to room temperature and the toluene was removed underreduced pressure. The residue was dissolved in CH₂Cl₂ (12 mL), adsorbedto Celite® and purified by flash chromatography (SiO₂, 35 mL/min, 0→25EtOAc/hexanes) to provide tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-cyclopent-2-en-1-yloxy-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate(205 mg, 89%) as a mixture of diastereomers (about 1:1) in the form of awhite solid: IR (thin film) 2928, 1755, 1709, 1117 cm⁻¹; ¹H NMR (400MHz, CDCl₃) δ 8.09 (m, 1H), 7.82 (m, 1H), 7.74-7.66 (m, 1H), 7.53-7.39(m, 2H), 7.42-7.28 (m, 2H), 6.13-6.01 (m, 1.5H), 6.01-5.92 (m, 0.5H),5.07 (app t, J=7.7 Hz, 1H), 4.90-4.79 (m, 2H), 4.02-3.83 (m, 2H), 3.76(dd, J=13.6, 2.8 Hz, 1H), 3.55-3.39 (m, 3H), 2.82-2.66 (m, 1H),2.60-2.47 (m, 1H), 2.34-2.17 (m, 2H), 2.11-1.92 (m, 3H), 1.57 (app dd,J=12.6, 6.4 Hz, 3H), 1.39 (app d, J=5.9 Hz, 18H); ESIMS m/z 618([M+Na]⁺).

Example 6 Step 2a-2: Preparation of tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-(cyclopentoxy)-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate(F132)

To a solution of tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-cyclopent-2-en-1-yloxy-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate(210 mg, 0.353 mmol) in EtOAc (3.5 mL) was added 10% Pd/C (37.5 mg,0.035 mmol). The reaction was put under a H₂ atmosphere (balloon) andstirred at room temperature for 5 h, whereupon the H₂ was purged fromsystem and the reaction was filtered through a pad of Celite®. The padwas washed with EtOAc (2×6 mL) and the organics were combined andconcentrated to dryness to afford tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-(cyclopentoxy)-9-methyl-7-(1-naphthyl-methyl)-2-oxo-1,5-dioxonan-3-yl]carbamate(193 mg, 92%) as a white powder: mp 49-55° C.; ¹H NMR (400 MHz, CDCl₃) δ8.09 (d, J=8.3 Hz, 1H), 7.82 (dd, J=8.1, 1.5 Hz, 1H), 7.74-7.67 (m, 1H),7.54-7.41 (m, 2H), 7.40-7.31 (m, 2H), 5.05 (app t, J=7.7 Hz, 1H),4.90-4.79 (m, 1H), 4.21-4.12 (m, 1H), 3.94 (dd, J=11.7, 7.5 Hz, 1H),3.88 (dd, J=11.7, 8.0 Hz, 1H), 3.73 (dd, J=13.6, 2.9 Hz, 1H), 3.53-3.35(m, 3H), 2.71 (app t, J=12.8 Hz, 1H), 2.07-1.96 (m, 1H), 1.90-1.70 (m,6H), 1.63-1.49 (m, 5H), 1.38 (s, 18H); ESIMS m/z 620 ([M+Na]⁺).

Example 6 Step 2b: Preparation of[(3S,6S,7R,8S)-3-[bis(tert-butoxycarbonyl)amino]-6-methyl-8-(1-naphthylmethyl)-4-oxo-1,5-dioxonan-7-yl]2-methylpropanoate(F128)

To a solution of tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-hydroxy-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate(290 mg, 0.548 mmol) and DMAP (201 mg, 1.64 mmol) in CH₂Cl₂ (2.7 mL) wasadded isobutyryl chloride (86 μL, 0.821 mmol) slowly to the flask andthe resulting solution was stirred at room temperature for 20 h. Thereaction mixture was dissolved in CH₂Cl₂ (4 mL), treated with Celite®,the solvent evaporated, and the adsorbed crude material purified byflash chromatography (SiO₂, 0→15% EtOAc/hexanes) to provide[(3S,6S,7R,8S)-3-[bis(tert-butoxycarbonyl)amino]-6-methyl-8-(1-naphthylmethyl)-4-oxo-1,5-dioxonan-7-yl]2-methylpropanoate(270 mg, 82%) as a white powder: mp 130-132° C.; ¹H NMR (400 MHz, CDCl₃)δ 8.01-7.93 (m, 1H), 7.84 (dd, J=8.0, 1.5 Hz, 1H), 7.72 (d, J=8.1 Hz,1H), 7.54-7.41 (m, 2H), 7.37 (dd, J=8.2, 7.0 Hz, 1H), 7.28 (dd, J=7.0,1.3 Hz, 1H), 5.20 (dd, J=8.7, 5.7 Hz, 1H), 5.11 (app t, J=9.3 Hz, 1H),5.08-4.97 (m, 1H), 4.06 (dd, J=11.8, 5.7 Hz, 1H), 3.86 (dd, J=11.9, 8.7Hz, 1H), 3.66 (d, J=11.0 Hz, 1H), 3.50 (dd, J=10.8, 6.4 Hz, 1H), 3.23(dd, J=14.0, 3.1 Hz, 1H), 2.74-2.55 (m, 2H), 2.37-2.20 (m, 1H), 1.42 (s,18H), 1.37 (d, J=6.2 Hz, 3H), 1.26 (app dd, J=7.0, 4.4 Hz, 6H); ESIMSm/z 622 ([M+Na]⁺).

Example 6 Step 2c: Preparation of tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-9-methyl-8-(4-methylphenoxy)-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate(F131)

To a solution of tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-8-hydroxy-9-methyl-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate(150 mg, 0.283 mmol), tritoluylbismuth diacetate (255 mg, 0.425 mmol),and diacetoxycopper (7.72 mg, 0.042 mmol) was addedN-cyclohexyl-N-methylcyclohexanamine (120 μL, 0.566 mmol). The mixturewas warmed to 50° C. and stirring continued at this temperature for 14h. The resulting thick slurry, was cooled to room temperature and loadeddirectly onto a silica gel precolumn and purified by flashchromatography (SiO₂, 30 mL/min, 0% EtOAc 1 min, 0→50% EtOAc/hexanes) toafford tert-butylN-tert-butoxycarbonyl-N-[(3S,7S,8R,9S)-9-methyl-8-(4-methylphenoxy)-7-(1-naphthylmethyl)-2-oxo-1,5-dioxonan-3-yl]carbamate(45 mg, 26%) as a colorless solid: ¹H NMR (400 MHz, CDCl₃) δ 8.11-8.03(m, 1H), 7.81 (dd, J=7.9, 1.6 Hz, 1H), 7.69 (d, J=8.1 Hz, 1H), 7.54-7.39(m, 2H), 7.39-7.30 (m, 1H), 7.27 (dd, J=7.0, 1.4 Hz, 1H), 7.16-7.08 (m,2H), 7.03-6.95 (m, 2H), 5.17 (dd, J=8.7, 6.5 Hz, 1H), 5.09-4.99 (m, 1H),4.40 (app t, J=9.0 Hz, 1H), 4.08 (dd, J=11.7, 6.6 Hz, 1H), 3.91 (dd,J=11.7, 8.7 Hz, 1H), 3.63-3.48 (m, 3H), 2.69-2.64 (m, 1H), 2.37-2.26 (m,4H), 1.47-1.38 (m, 21H); ¹³C NMR (101 MHz, CDCl₃) δ 169.99, 157.28,152.59, 135.48, 133.98, 131.99, 130.55, 130.22, 128.67, 127.79, 127.09,125.91, 125.43, 125.14, 124.04, 115.18, 83.05, 82.23, 75.40, 72.08,70.65, 57.24, 46.50, 32.68, 27.84, 20.43, 19.10; ESIMS m/z 642([M+Na]⁺).

Example 6 Steps 3a and 3b: Preparation of(3S,6S,7R,8S)-3-(3-hydroxy-4-methoxypicolin-amido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-ylisobutyrate (F5)

Step 3a

To a solution of[(3S,6S,7R,8S)-3-[bis(tert-butoxycarbonyl)amino]-6-methyl-8-(1-naphthylmethyl)-4-oxo-1,5-dioxonan-7-yl]2-methylpropanoate(260 mg, 0.434 mmol) in CH₂Cl₂ (1 mL) was added 4 M HCl in dioxane (2.17mL, 8.67 mmol) slowly (gas evolution) and the resulting solution wasstirred at room temperature for 2.5 h. The solvent was evaporated undera stream of N₂ to give(3S,7S,8R,9S)-8-(isobutyryloxy)-9-methyl-7-(naphthalen-1-ylmethyl)-2-oxo-1,5-dioxonan-3-aminiumchloride as a white powder. The powder was dried under high vacuum for20 h to remove residual HCl and was used without further purificationfor the amide picolinamide formation: ESIMS m/z 400 ([M+H]⁺).

Step 3b

To a suspension of(3S,7S,8R,9S)-8-(isobutyryloxy)-9-methyl-7-(naphthalen-1-ylmethyl)-2-oxo-1,5-dioxonan-3-aminiumchloride in CH₂Cl₂ (2 mL) were added PyBOP (248 mg, 0.477 mmol) and3-hydroxy-4-methoxypicolinic acid (81 mg, 0.477 mmol) followed by thedropwise addition of N-ethyl-N-isopropylpropan-2-amine (249 μl, 1.43mmol). After 10 min everything solubilized and stirring was continuedfor 2 h. The reaction was treated with Celite®, the solvent removedunder reduced pressure, and the resulting adsorbed crude material waspurified by flash chromatography (SiO₂, 0→100% EtOAc/hexanes) to provide(3S,6S,7R,8S)-3-(3-hydroxy-4-methoxypicolin-amido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-ylisobutyrate as a white powder (210 mg, 88%): mp 139-142° C.; ¹H NMR (400MHz, CDCl₃) δ 11.91 (s, 1H), 8.50 (d, J=8.3 Hz, 1H), 8.01-7.92 (m, 2H),7.89-7.82 (m, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.49 (dddd, J=14.7, 8.1, 6.9,1.5 Hz, 2H), 7.40 (dd, J=8.2, 7.0 Hz, 1H), 7.30 (dd, J=6.9, 1.2 Hz, 1H),6.84 (d, J=5.2 Hz, 1H), 5.20-5.02 (m, 3H), 4.04 (dd, J=11.7, 7.3 Hz,1H), 3.92 (s, 3H), 3.60 (d, J=4.1 Hz, 2H), 3.43 (dd, J=11.7, 7.1 Hz,1H), 3.23 (dd, J=14.2, 3.2 Hz, 1H), 2.79-2.64 (m, 2H), 2.36-2.23 (m,1H), 1.43-1.37 (m, 3H), 1.29 (dd, J=7.0, 3.6 Hz, 6H); ¹³C NMR (101 MHz,CDCl₃) δ 176.37, 171.12, 168.88, 155.32, 148.71, 140.60, 134.68, 133.97,131.94, 130.09, 128.97, 127.76, 127.35, 126.02, 125.57, 125.37, 123.45,109.55, 76.95, 74.38, 72.09, 56.07, 51.42, 44.93, 34.37, 32.19, 19.14,19.07, 18.26; HRMS-ESI (m/z) [M+H]⁺ calcd for C₃₀H₃₅N₂O₈ expected,551.2388. found 551.2388.

Example 7 Preparation of(3S,6S,7R,8S)-3-(3-(acetoxymethoxy)-4-methoxypicolin-amido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-ylisobutyrate (F83)

To a mixture of(3S,6S,7R,8S)-3-(3-hydroxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-ylisobutyrate (85 mg, 0.154 mmol) and K₂CO₃ (42.7 mg, 0.309 mmol) inacetone (2.0 mL) was added bromomethyl acetate (21.2 μL, 0.216 mmol),and the reaction was stirred vigorously at 50° C. under N₂ for 1 h. Thereaction was cooled to room temperature, diluted with CH₂Cl₂ (10 mL),filtered, and treated with Celite®. The solvent was removed underreduced pressure and the resulting adsorbed crude material was purifiedby flash chromatography (SiO₂, 0→50% acetone/hexanes) to afford(3S,6S,7R,8S)-3-(3-(acetoxymethoxy)-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-ylisobutyrate (70 mg, 0.112 mmol, 73% yield) as a white powder: mp 58-64°C.; ¹H NMR (400 MHz, CDCl₃) δ 8.37 (d, J=8.1 Hz, 1H), 8.24 (d, J=5.3 Hz,1H), 8.02-7.94 (m, 1H), 7.89-7.81 (m, 1H), 7.74 (d, J=8.2 Hz, 1H),7.56-7.43 (m, 2H), 7.40 (dd, J=8.2, 7.0 Hz, 1H), 7.30 (dd, J=7.1, 1.2Hz, 1H), 6.92 (d, J=5.4 Hz, 1H), 5.71 (d, J=6.5 Hz, 2H), 5.17-5.06 (m,3H), 4.04 (dd, J=11.6, 7.4 Hz, 1H), 3.89 (s, 3H), 3.60 (d, J=4.2 Hz,2H), 3.40 (dd, J=11.7, 7.1 Hz, 1H), 3.23 (dd, J=14.2, 3.1 Hz, 1H),2.77-2.63 (m, 2H), 2.29 (ddt, J=12.2, 8.1, 3.9 Hz, 1H), 2.04 (s, 3H),1.39 (d, J=5.6 Hz, 3H), 1.29 (dd, J=7.0, 3.9 Hz, 6H); ¹³C NMR (101 MHz,CDCl₃) δ 176.38, 171.75, 170.27, 163.15, 160.19, 145.74, 143.97, 142.01,134.75, 133.97, 131.96, 128.95, 127.78, 127.32, 125.99, 125.54, 125.38,123.50, 109.70, 89.40, 74.18, 72.32, 71.93, 56.18, 51.77, 44.97, 34.38,32.25, 20.85, 19.14, 19.07, 18.28; HRMS-ESI (m/z) [M+H]+calcd forC₃₃H₃₉N₂O₁₀ expected, 623.2599. found, 623.2611.

Example 8 Preparation of(3S,6S,7R,8S)-3-(3-acetoxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-ylisobutyrate (F51)

To a solution of(3S,6S,7R,8S)-3-(3-hydroxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-ylisobutyrate (80 mg, 0.145 mmol) and DMAP (28.4 mg, 0.232 mmol) in CH₂Cl₂(1.45 mL) was added acetyl chloride (218 μL, 0.218 mmol) slowly and theresulting mixture was stirred at room temperature for 14 h. The reactionmixture was treated with Celite®, the solvent removed under reducedpressure, and the resulting adsorbed crude material was purified byflash chromatography (SiO₂, 0→100% acetone/hexanes) to afford(3S,6S,7R,8S)-3-(3-acetoxy-4-methoxypicolinamido)-6-methyl-8-(naphthalen-1-ylmethyl)-4-oxo-1,5-dioxonan-7-ylisobutyrate as a white powder (80 mg, 93%): mp 104-108° C.; ¹H NMR (400MHz, CDCl₃) δ 8.53 (d, J=8.2 Hz, 1H), 8.27 (d, J=5.4 Hz, 1H), 8.01-7.94(m, 1H), 7.88-7.81 (m, 1H), 7.73 (d, J=8.2 Hz, 1H), 7.55-7.43 (m, 2H),7.39 (dd, J=8.2, 7.0 Hz, 1H), 7.29 (dd, J=7.0, 1.2 Hz, 1H), 6.96 (d,J=5.4 Hz, 1H), 5.18-5.02 (m, 3H), 4.00 (dd, J=11.7, 7.4 Hz, 1H), 3.86(s, 3H), 3.58 (d, J=4.2 Hz, 2H), 3.37 (dd, J=11.7, 7.2 Hz, 1H), 3.22(dd, J=14.1, 3.1 Hz, 1H), 2.76-2.63 (m, 2H), 2.38 (s, 3H), 2.34-2.22 (m,1H), 1.38 (d, J=5.7 Hz, 3H), 1.29 (d, J=3.7 Hz, 3H), 1.27 (d, J=3.7 Hz,3H); ¹³C NMR (101 MHz, CDCl₃) δ 176.38, 171.66, 168.84, 162.67, 159.42,146.73, 141.03, 137.53, 134.77, 133.99, 131.98, 128.97, 127.78, 127.34,126.01, 125.57, 125.39, 123.50, 109.95, 77.05, 74.20, 72.26, 71.84,56.29, 51.51, 44.99, 34.38, 32.26, 20.73, 19.15, 19.08, 18.28; HRMS-ESI(m/z) [M+H]+calcd for C₃₂H₃₇N₂O₉ expected, 593.2494. found, 593.2502.

Example 9 Preparation of((4-methoxy-2-(((3S,7S,8R,9S)-9-methyl-2-oxo-8-propoxy-7-(4-(trifluoromethyl)benzyl)-1,5-dioxonan-3-yl)carbamoyl)pyridin-3-yl)oxy)methyl2-ethoxyacetate (F120)

To a solution of3-hydroxy-4-methoxy-N-((3S,7S,8R,9S)-9-methyl-2-oxo-8-propoxy-7-(4-(trifluoromethyl)benzyl)-1,5-dioxonan-3-yl)picolinamide(83 mg, 0.154 mmol) in acetone (2 mL) were added Na₂CO₃ (24.4 mg, 0.230mmol), NaI (4.60 mg, 0.031 mmol), and chloromethyl 2-ethoxyacetate (30.5mg, 0.200 mmol), and the mixture was stirred for 7 hours at 40° C. Thereaction was cooled to room temperature and purified directly by flashchromatography (SiO₂, 0→100% EtOAc/hexanes) to give((4-methoxy-2-(((3S,7S,8R,9S)-9-methyl-2-oxo-8-propoxy-7-(4-(trifluoromethyl)benzyl)-1,5-dioxonan-3-yl)carbamoyl)pyridin-3-yl)oxy)methyl2-ethoxyacetate as a colorless oil (94 mg, 93%): ¹H NMR (400 MHz, CDCl₃)δ 8.41 (d, J=8.2 Hz, 1H), 8.26 (d, J=5.4 Hz, 1H), 7.61-7.50 (m, 2H),7.32 (d, J=8.0 Hz, 2H), 6.95 (d, J=5.4 Hz, 1H), 5.80 (s, 2H), 5.04-4.95(m, 2H), 4.08 (s, 2H), 4.03 (dd, J=11.7, 7.3 Hz, 1H), 3.90 (s, 3H), 3.66(dt, J=8.6, 6.6 Hz, 1H), 3.63-3.47 (m, 3H), 3.47-3.36 (m, 3H), 3.23-3.12(m, 2H), 2.43 (dd, J=13.7, 11.7 Hz, 1H), 2.01-1.90 (m, 1H), 1.69-1.58(m, 2H), 1.51 (d, J=6.4 Hz, 3H), 1.22 (t, J=7.0 Hz, 3H), 0.97 (t, J=7.4Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −62.35; HRMS-ESI (m/z) [M]⁺ calcdfor C₃₁H₃₉F₃N₂O₁₀ expected, 656.2557. found, 656.2569.

Example A Evaluation of Fungicidal Activity: Leaf Blotch of Wheat(Mycosphaerella graminicola; Anamorph: Septoria tritici; Bayer codeSEPTTR)

Technical grades of materials were dissolved in acetone, which were thenmixed with nine volumes of water containing 110 ppm Triton X-100. Thefungicide solutions were applied onto wheat seedlings using an automatedbooth sprayer to run-off. All sprayed plants were allowed to air dryprior to further handling. All fungicides were evaluated using theaforementioned method for their activity vs. all target diseases. Wheatleaf blotch and brown rust activity were also evaluated using trackspray applications, in which case the fungicides were formulated as ECformulations, containing 0.1% Trycol 5941 in the spray solutions.

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50%mineral soil/50% soil-less Metro mix until the first leaf was fullyemerged, with 7-10 seedlings per pot. These plants were inoculated withan aqueous spore suspension of Septoria tritici either prior to or afterfungicide treatments. After inoculation the plants were kept in 100%relative humidity (one day in a dark dew chamber followed by two tothree days in a lighted dew chamber at 20° C.) to permit spores togerminate and infect the leaf. The plants were then transferred to agreenhouse set at 20° C. for disease to develop. When disease symptomswere fully expressed on the 1^(st) leaves of untreated plants, infectionlevels were assessed on a scale of 0 to 100 percent disease severity.Percent disease control was calculated using the ratio of diseaseseverity on treated plants relative to untreated plants.

Example B Evaluation of Fungicidal Activity: Wheat Brown Rust (Pucciniatriticina; Synonym: Puccinia recondite f sp. tritici; Bayer code PUCCRT)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50%mineral soil/50% soil-less Metro mix until the first leaf was fullyemerged, with 7-10 seedlings per pot. These plants were inoculated withan aqueous spore suspension of Puccinia triticina either prior to orafter fungicide treatments. After inoculation the plants were kept in adark dew room at 22° C. with 100% relative humidity overnight to permitspores to germinate and infect the leaf. The plants were thentransferred to a greenhouse set at 24° C. for disease to develop.Fungicide formulation, application and disease assessment followed theprocedures as described in the Example A.

Example C Evaluation of Fungicidal Activity: Wheat Glume Blotch(Leptosphaeria nodorum; Bayer code LEPTNO)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50%mineral soil/50% soil-less Metro mix until the first leaf was fullyemerged, with 7-10 seedlings per pot. These plants were inoculated withan aqueous spore suspension of Leptosphaeria nodorum 24 hr afterfungicide treatments. After inoculation the plants were kept in 100%relative humidity (one day in a dark dew chamber followed by two days ina lighted dew chamber at 20° C.) to permit spores to germinate andinfect the leaf. The plants were then transferred to a greenhouse set at20° C. for disease to develop. Fungicide formulation, application anddisease assessment followed the procedures as described in the ExampleA.

Example D Evaluation of Fungicidal Activity: Apple Scab (Venturiainaequalis; Bayer code VENTIN)

Apple seedlings (variety McIntosh) were grown in soil-less Metro mix,with one plant per pot. Seedlings with two expanding young leaves at thetop (older leaves at bottom of the plants were trimmed) were used in thetest. Plants were inoculated with a spore suspension of Venturiainaequalis 24 hr after fungicide treatment and kept in a 22° C. dewchamber with 100% RH for 48 hr, and then moved to a greenhouse set at20° C. for disease to develop. Fungicide formulation, application anddisease assessment on the sprayed leaves followed the procedures asdescribed in the Example A.

Example E Evaluation of Fungicidal Activity: Grape Powdery Mildew(Uncinula necator; Bayer code UNCINE)

Grape seedlings (variety Carignane) were grown in soil-less Metro mix,with one plant per pot, and used in the test when approximately onemonth old. Plants were inoculated 24 hr after fungicide treatment byshaking spores from infected leaves over test plants. Plants weremaintained in a greenhouse set at 20° C. until disease was fullydeveloped. Fungicide formulation, application and disease assessment onthe sprayed leaves followed the procedures as described in the ExampleA.

Example F Evaluation of Fungicidal Activity: Powdery Mildew of Cucumber(Erysiphe cichoracearum; Bayer code ERYSCI)

Cucumber seedlings (variety Bush Pickle) were grown in soil-less Metromix, with one plant per pot, and used in the test when 12 to 14 daysold. Plants were inoculated with a spore suspension 24 hr followingfungicide treatments. After inoculation the plants remained in thegreenhouse set at 20° C. until disease was fully expressed. Fungicideformulation, application and disease assessment on the sprayed leavesfollowed the procedures as described in the Example A.

Example G Evaluation of Fungicidal Activity: Leaf Spot of Sugar Beets(Cercospora beticola; Bayer Code CERCBE)

Sugar beet plants (variety HH88) were grown in soil-less Metro mix andtrimmed regularly to maintain a uniform plant size prior to test. Plantswere inoculated with a spore suspension 24 hr after fungicidetreatments. Inoculated plants were kept in a dew chamber at 22° C. for48 hr then incubated in a greenhouse set at 24° C. under a clear plastichood with bottom ventilation until disease symptoms were fullyexpressed. Fungicide formulation, application and disease assessment onthe sprayed leaves followed the procedures as described in the ExampleA.

Example H Evaluation of Fungicidal Activity: Asian Soybean Rust(Phakopsora pachyrhizi; Bayer code PHAKPA)

Technical grades of materials were dissolved in acetone, which were thenmixed with nine volumes of water containing 0.011% Tween 20. Thefungicide solutions were applied onto soybean seedlings using anautomated booth sprayer to run-off. All sprayed plants were allowed toair dry prior to further handling.

Soybean plants (variety Williams 82) were grown in soil-less Metro mix,with one plant per pot. Two weeks old seedlings were used for testing.Plants were inoculated either 3 days prior to or 1 day after fungicidetreatments. Plants were incubated for 24 h in a dark dew room at 22° C.and 100% RH then transferred to a growth room at 23° C. for disease todevelop. Disease severity was assessed on the sprayed leaves.

Example I Evaluation of Fungicidal Activity: Wheat Powdery Mildew(Blumeria graminis f.sp. tritici; Synonym: Erysiphe graminis f.sp.tritici; Bayer code ERYSGT)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50%mineral soil/50% soil-less Metro mix until the first leaf was fullyemerged, with 7-10 seedlings per pot. These plants were inoculated bydusting with infected stock plants 24 hr after fungicide treatments.After inoculation the plants were kept in a greenhouse set at 20° C. fordisease to develop. Fungicide formulation, application and diseaseassessment on the sprayed leaves followed the procedures as described inthe Example A.

Example J Evaluation of Fungicidal Activity: Barley Powdery Mildew(Blumeria graminis fsp. hordei; Synonym: Erysiphe graminis fsp. hordei;Bayer Code ERYSGH)

Barley seedlings (variety Harrington) were propagated in soil-less Metromix, with each pot having 8 to 12 plants, and used in the test whenfirst leaf was fully emerged. Test plants were inoculated by dustingwith infected stock plants 24 hr after fungicide treatments. Afterinoculation the plants were kept in a greenhouse set at 20° C. fordisease to develop. Fungicide formulation, application and diseaseassessment on the sprayed leaves followed the procedures as described inthe Example A.

Example K Evaluation of Fungicidal Activity: Barley Scald (Rhyncosporiumsecalis; Bayer Code RHYNSE)

Barley seedlings (variety Harrington) were propagated in soil-less Metromix, with each pot having 8 to 12 plants, and used in the test whenfirst leaf was fully emerged. Test plants were inoculated by an aqueousspore suspension of Rhyncosporium secalis 24 hr after fungicidetreatments. After inoculation the plants were kept in a dew room at 20°C. with 100% relative humidity for 48 hr. The plants were thentransferred to a greenhouse set at 20° C. for disease to develop.Fungicide formulation, application and disease assessment on the sprayedleaves followed the procedures as described in the Example A.

Example L Evaluation of Fungicidal Activity: Rice Blast (Magnaporthegrisea; Anamorph: Pyricularia oryzae; Bayer Code PYRIOR)

Rice seedlings (variety Japonica) were propagated in soil-less Metromix, with each pot having 8 to 14 plants, and used in the test when 12to 14 days old. Test plants were inoculated with an aqueous sporesuspension of Pyricularia oryzae 24 hr after fungicide treatments. Afterinoculation the plants were kept in a dew room at 22° C. with 100%relative humidity for 48 hr to permit spores to germinate and infect theleaf. The plants were then transferred to a greenhouse set at 24° C. fordisease to develop. Fungicide formulation, application and diseaseassessment on the sprayed leaves followed the procedures as described inthe Example A.

Example M Evaluation of Fungicidal Activity: Tomato Early Blight(Alternaria solani; Bayer Code ALTESO)

Tomato plants (variety Outdoor girl) were propagated in soil-less Metromix, with each pot having one plant, and used when 12 to 14 days old.Test plants were inoculated with an aqueous spore suspension ofAlternaria solani 24 hr after fungicide treatments. After inoculationthe plants were kept in 100% relative humidity (one day in a dark dewchamber followed by two to three days in a lighted dew chamber at 20°C.) to permit spores to germinate and infect the leaf. The plants werethen transferred to a growth room at 22° C. for disease to develop.Fungicide formulation, application and disease assessment on the sprayedleaves followed the procedures as described in the Example A.

Example N Evaluation of Fungicidal Activity: Cucumber Anthracnose(Glomerella lagenarium; Anamorph: Colletotrichum lagenarium; Bayer CodeCOLLLA)

Cucumber seedlings (variety Bush Pickle) were propagated in soil-lessMetro mix, with each pot having one plant, and used in the test when 12to 14 days old. Test plants were inoculated with an aqueous sporesuspension of Colletotrichum lagenarium 24 hr after fungicidetreatments. After inoculation the plants were kept in a dew room at 22°C. with 100% relative humidity for 48 hr to permit spores to germinateand infect the leaf. The plants were then transferred to a growth roomset at 22° C. for disease to develop. Fungicide formulation, applicationand disease assessment on the sprayed leaves followed the procedures asdescribed in the Example A.

TABLE 1 Compound Structure and Appearance Prepared According Compound toNumber Structure Example Appearance F1 

Example 6, Step 3b White powder F2 

Example 6, Step 3b White Solid F3 

Example 6, Step 3b White Solid F4 

Example 6, Step 3b White Powder F5 

Example 6, Step 3b White Powder F6 

Example 6, Step 3b White Solid F7 

Example 6, Step 3b White Powder F8 

Example 6, Step 3b White Solid F9 

Example 6, Step 3b White Powder F10 

Example 6, Step 3b White Solid F11 

Example 6, Step 3b White Powder F12 

Example 6, Step 3b White Powder F13 

Example 6, Step 3b White Powder F14 

Example 6, Step 3b White Powder F15 

Example 6, Step 3b Colorless Oil F16 

Example 6, Step 3b Colorless Oil F17 

Example 6, Step 3b Colorless Oil F18 

Example 6, Step 3b Colorless Oil F19 

Example 6, Step 3b Colorless Oil F20 

Example 6, Step 3b Colorless Film F21 

Example 5, Step 1b Colorless Oil F22 

Example 6, Step 3b Colorless Oil F23 

Example 6, Step 3b Colorless Oil F24 

Example 6, Step 3b Colorless Oil F25 

Example 6, Step 3b Colorless Oil F26 

Example 6, Step 3b Colorless Amorphous Solid F27 

Example 6, Step 3b Colorless Oil F28 

Example 6, Step 3b Colorless Oil F29 

Example 6, Step 3b Colorless Oil F30 

Example 6, Step 3b Colorless Oil F31 

Example 6, Step 3b Colorless Oil F32 

Example 6, Step 3b Colorless Oil F33 

Example 6, Step 3b Colorless Solid F34 

Example 6, Step 3b Colorless Oil F35 

Example 6, Step 3b Colorless Solid F36 

Example 6, Step 3b Colorless Oil F37 

Example 6, Step 3b Colorless Oil F38 

Example 6, Step 3b Colorless Solid F39 

Example 6, Step 3b Colorless Oil F40 

Example 5, Step 1b Colorless Oil F41 

Example 6, Step 3b White Solid F42 

Example 6, Step 3b White Solid F43 

Example 6, Step 3b White Solid F44 

Example 6, Step 3b White Solid F45 

Example 6, Step 3b White Solid F46 

Example 6, Step 3b White Solid F47 

Example 6, Step 3b White Solid F48 

Example 5, Step 1b White Foam F49 

Example 8 White Powder F50 

Example 8 White Solid F51 

Example 8 White Powder F52 

Example 8 White Powder F53 

Example 8 Sticky White Solid F54 

Example 8 White Powder F55 

Example 8 Colorless Oil F56 

Example 8 White Powder F57 

Example 8 White Solid F58 

Example 8 Colorless Amorphous Solid F59 

Example 8 Colorless Oil F60 

Example 8 Colorless Oil F61 

Example 8 Colorless Amorphous Solid F62 

Example 8 Colorless Oil F63 

Example 8 Colorless Amorphous Solid F64 

Example 8 Colorless Film F65 

Example 8 Colorless Oil F66 

Example 8 Colorless Amorphous Solid F67 

Example 8 Colorless Oil F68 

Example 8 Colorless Oil F69 

Example 8 Colorless Oil F70 

Example 8 Colorless Oil F71 

Example 8 Colorless Oil F72 

Example 8 Colorless Oil F73 

Example 8 White Solid F74 

Example 8 White Solid F75 

Example 8 White Solid F76 

Example 8 White Solid F77 

Example 8 White Solid F78 

Example 8 White Solid F79 

Example 8 White Solid F80 

Example 8 White Foam F81 

Example 7 White Powder F82 

Example 7 Viscous Oil F83 

Example 7 White Powder F84 

Example 7 White Powder F85 

Example 7 White Solid F86 

Example 7 Slightly Yellow Oil F87 

Example 7 Colorless Oil F88 

Example 7 White Powder F89 

Example 7 White Powder F90 

Example 7 White Powder F91 

Example 7 White Powder F92 

Example 7 Colorless Oil F93 

Example 7 Colorless Oil F94 

Example 7 Colorless Oil F95 

Example 7 Colorless Oil F96 

Example 7 Colorless Oil F97 

Example 7 Colorless Oil F98 

Example 7 Colorless Oil F99 

Example 7 Colorless Oil F100

Example 7 Colorless Oil F101

Example 7 Colorless Oil F102

Example 7 Colorless Oil F103

Example 7 Colorless Oil F104

Example 7 Pale Pink Oil F105

Example 7 Colorless Oil F106

Example 7 Colorless Oil F107

Example 7 Colorless Oil F108

Example 7 Colorless Oil F109

Example 7 Colorless Oil F110

Example 7 White Solid F111

Example 7 White Solid F112

Example 7 Yellow Solid F113

Example 7 White Solid F114

Example 7 Yellow Solid F115

Example 7 Sticky Yellow Solid F116

Example 7 Yellow Oil F117

Example 7 White Foam F118

Example 7 Colorless Oil F119

Example 7 White Solid F120

Example 9 Colorless Oil F121

Example 9 Clear Gel F122

Example 9 Clear Gel F123

Example 8 White Solid F124

Example 6, Step 2a-2 Colorless Oil F125

Example 6, Step 2a-2 Oil F126

Example 6, Step 2a-2 Colorless Oil F127

Example 6, Step 2a-2 Colorless Oil F128

Example 6, Step 2b White Powder F129

Example 6, Step 2a-2 Off-White Solid F130

Example 6, Step 2a-2 Colorless Oil F131

Example 6, Step 2c Colorless Solid F132

Example 6, Step 2a-2 White Powder F133

Example 6, Step 2a-2 White Powder F134

Example 6, Step 2a-2 White Solid F135

Example 6, Step 2b White Powder F136

Example 6, Step 2b White Solid F137

Example 6, Step 2b White Solid F138

Example 6, Step 2b Colorless Oil F139

Example 6, Step 2c Colorless Film F140

Example 6, Step 2a-2 Colorless Oil F141

Example 6, Step 2a-2 Colorless Oil F142

Example 6, Step 2a-2 Colorless Oil F143

Example 4, Step 1 Colorless Oil F144

Example 6, Step 2b Colorless Oil F145

Example 6, Step 2a-2 Colorless Oil F146

Example 6, Step 2c Colorless Film F147

Example 6, Step 2a-2 Colorless Oil F148

Example 6, Step 2b Colorless Oil F149

Example 6, Step 2a-2 Colorless Oil F150

Example 6, Step 2a-2 Colorless Oil F151

Example 6, Step 2a-2 Colorless Oil F152

Example 6, Step 2b Colorless Oil F153

Example 6, Step 2a-2 Colorless Oil F154

Example 6, Step 2a-2 Colorless Oil F155

Example 6, Step 2a-2 Colorless Oil F156

Example 6, Step 2a-2 Colorless Oil F157

Example 6, Step 2a-2 Colorless Oil F158

Example 6, Step 2b Colorless Oil F159

Example 6, Step 2c Colorless Oil F160

Example 6, Step 2a-2 Colorless Oil F161

Example 6, Step 2a-2 Colorless Oil F162

Example 4, Step 1 Colorless Oil F163

Example 6, Step 2b White Solid F164

Example 6, Step 2a-2 Sticky White Solid F165

Example 6, Step 2a-2 Clear Gel F166

Example 6, Step 2c Clear Oil F167

Example 6, Step 2b White Solid F168

Example 6, Step 2a-2 Clear Oil F169

Example 6, Step 2a-2 Clear Oil F170

Example 4, Step 1 Colorless, Sticky Oil. F171

Example 6, Step 3a White Solid F172

Example 6, Step 3a White Solid F173

Example 6, Step 3a White Solid F174

Example 6, Step 3a White Powder F175

Example 6, Step 3a White Powder F176

Example 6, Step 3a White Powder F177

Example 6, Step 3a White Powder F178

Example 6, Step 3a White Solid F179

Example 6, Step 3a White Powder F180

Example 6, Step 3a White Powder F181

Example 6, Step 3a White Solid F182

Example 6, Step 3a White Powder F183

Example 6, Step 3a White Powder F184

Example 6, Step 3a White Powder F185

Example 6, Step 3a Colorless Oil F186

Example 6, Step 3a — F187

Example 6, Step 3a — F188

Example 6, Step 3a — F189

Example 6, Step 3a Colorless Film F190

Example 6, Step 3a Colorless Oil F191

Example 5, Step 1a White Solid F192

Example 6, Step 3a Pale Yellow Amorphous Solid F193

Example 6, Step 3a — F194

Example 6, Step 3a — F195

Example 6, Step 3a Colorless Film F196

Example 6, Step 3a — F197

Example 6, Step 3a Colorless Oil F198

Example 6, Step 3a Colorless Oil F199

Example 6, Step 3a Colorless Oil F200

Example 6, Step 3a Colorless Oil F201

Example 6, Step 3a Colorless Film F202

Example 6, Step 3a Colorless Oil F203

Example 6, Step 3a Colorless Oil F204

Example 6, Step 3a Colorless Semi Solid F205

Example 6, Step 3a Colorless Oil F206

Example 6, Step 3a Colorless Oil F207

Example 6, Step 3a Colorless Film F208

Example 6, Step 3a — F209

Example 6, Step 3a Colorless Film F210

Example 5, Step 1a Colorless Solid F211

Example 6, Step 3a White Solid F212

Example 6, Step 3a White Solid F213

Example 6, Step 3a White Solid F214

Example 6, Step 3a Tan Solid F215

Example 6, Step 3a White Solid F216

Example 6, Step 3a White Solid F217

Example 6, Step 3a White Solid F218

Example 5, Step 1a White Solid

TABLE 2 Analytical Data Cmpd No. MP (° C.) IR (cm⁻¹) Mass ¹H NMR ¹³C or¹⁹F NMR F1 51-58 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.99 (s, — (m/z) 1H), 8.64(d, J = 8.2 Hz, 1H), [M + H]⁺ 7.99 (d, J = 5.2 Hz, 1H), 7.33- calcd for7.24 (m, 2H), 7.22-7.14 C₂₈H₃₇N₂O₇, (m, 3H), 6.86 (d, J = 5.2 Hz,513.2595; 1H), 5.07-4.90 (m, 2H), 4.14 found, (dd, J = 11.8, 6.4 Hz,1H), 513.2600 4.01-3.90 (m, 4H), 3.73 (dd, J = 11.4, 1.8 Hz, 1H), 3.68-3.58 (m, 2H), 3.23 (app t, J = 8.2 Hz, 1H), 2.76 (ddd, J = 13.7, 11.0,4.7 Hz, 1H), 2.60 (ddd, J = 13.7, 10.3, 6.2 Hz, 1H), 2.10-1.96 (m, 1H),1.79- 1.37 (m, 13H) F2 78-81 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.95 (s, —(m/z) 1H), 8.62 (d, J = 8.3 Hz, 1H), [M + H]⁺ 8.00 (d, J = 5.2 Hz, 1H),7.34- calcd for 7.24 (m, 2H), 7.24-7.14 C₂₇H₃₄F₃N₂O₇, (m, 3H), 6.87 (d,J = 5.2 Hz, 555.2313; 1H), 5.07-4.92 (m, 2H), 4.12 found, (dd, J = 11.8,7.0 Hz, 1H), 555.2327 3.94 (s, 3H), 3.73 (dd, J = 10.9, 1.8 Hz, 1H),3.68-3.60 (m, 2H), 3.60-3.53 (m, 1H), 3.53-3.45 (m, 1H), 3.10 (app t, J= 8.8 Hz, 1H), 2.79 (ddd, J = 14.3, 10.2, 4.8 Hz, 1H), 2.56 (ddd, J =13.7, 9.8, 6.8 Hz, 1H), 2.23-2.06 (m, 2H), 1.93- 1.83 (m, 1H), 1.83-1.74(m, 2H), 1.73-1.67 (m, 1H), 1.62-1.48 (m, 1H), 1.45 (d, J = 6.4 Hz, 3H)F3 96-98 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.98 (s, — (m/z) 1H), 8.65 (d, J =8.3 Hz, 1H), [M + H]⁺ 7.99 (d, J = 5.2 Hz, 1H), 7.33- calcd for 7.24 (m,2H), 7.23-7.14 C₂₈H₃₉N₂O₇, (m, 3H), 6.86 (d, J = 5.2 Hz, 515.2752; 1H),5.07-4.93 (m, 2H), 4.10 found, (dd, J = 11.7, 7.0 Hz, 1H), 515.2767 3.92(s, 3H), 3.76 (dd, J = 11.1, 1.6 Hz, 1H), 3.67 (dd, J = 11.8, 6.4 Hz,1H), 3.61 (dd, J = 11.0, 6.3 Hz, 1H), 3.57- 3.40 (m, 2H), 3.07 (app t, J= 9.0 Hz, 1H), 2.77 (ddd, J = 13.7, 10.9, 4.7 Hz, 1H), 2.57 (ddd, J =13.7, 10.4, 6.4 Hz, 1H), 2.06-1.90 (m, 1H), 1.77- 1.64 (m, 1H),1.60-1.48 (m, 3H), 1.47 (d, J = 6.3 Hz, 3H), 1.37-1.26 (m, 4H), 0.95-0.84 (m, 3H) F4 117-120 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.98 (s, — (m/z)1H), 8.64 (d, J = 8.2 Hz, 1H), [M + H]⁺ 8.00 (d, J = 5.2 Hz, 1H), 7.33-calcd for 7.24 (m, 2H), 7.23-7.15 C₂₇H₃₇N₂O₇, (m, 3H), 6.87 (d, J = 5.2Hz, 501.2595; 1H), 5.07-4.94 (m, 2H), 4.11 found (dd, J = 11.8, 7.0 Hz,1H), 501.2591 3.93 (s, 3H), 3.75 (dd, J = 11.0, 1.6 Hz, 1H), 3.70-3.58(m, 2H), 3.29 (dd, J = 8.3, 6.4 Hz, 1H), 3.23 (dd, J = 8.4, 6.4 Hz, 1H),3.07 (app t, J = 9.0 Hz, 1H), 2.77 (ddd, J = 13.6, 10.8, 4.7 Hz, 1H),2.57 (ddd, J = 13.7, 10.3, 6.6 Hz, 1H), 1.98 (dddd, J = 13.7, 10.9, 6.6,3.0 Hz, 1H), 1.89-1.65 (m, 2H), 1.58-1.43 (m, 4H), 0.90 (app d, J = 6.7Hz, 6H) F5 139-142 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.91 (s, — (m/z) 1H),8.50 (d, J = 8.3 Hz, 1H), [M + H]⁺ 8.01-7.92 (m, 2H), 7.89- calcd for7.82 (m, 1H), 7.74 (d, J = 8.2 C₃₀H₃₅N₂O₈, Hz, 1H), 7.49 (dddd, J =14.7, 551.2388; 8.1, 6.9, 1.5 Hz, 2H), 7.40 (dd, found J = 8.2, 7.0 Hz,1H), 7.30 (dd, 551.2388 J = 6.9, 1.2 Hz, 1H), 6.84 (d, J = 5.2 Hz, 1H),5.20-5.02 (m, 3H), 4.04 (dd, J = 11.7, 7.3 Hz, 1H), 3.92 (s, 3H), 3.60(d, J = 4.1 Hz, 2H), 3.43 (dd, J = 11.7, 7.1 Hz, 1H), 3.23 (dd, J =14.2, 3.2 Hz, 1H), 2.79- 2.64 (m, 2H), 2.36-2.23 (m, 1H), 1.43-1.37 (m,3H), 1.29 (dd, J = 7.0, 3.6 Hz, 6H) F6 118-122 — HRMS-ESI ¹H NMR (CDCl₃)δ 11.93 (s, — (m/z) 1H), 8.48 (d, J = 8.4 Hz, 1H), [M + H]⁺ 8.15-8.07(m, 1H), 7.93 (d, J = calcd for 5.2 Hz, 1H), 7.84 (dd, J = C₃₀H₃₄F₃N₂O7,7.6, 2.0 Hz, 1H), 7.73 (d, J = 591.2313; 8.1 Hz, 1H), 7.55-7.42 (m,found 2H), 7.39 (dd, J = 8.2, 6.9 Hz, 591.2315 1H), 7.32 (dd, J = 7.0,1.3 Hz, 1H), 6.81 (d, J = 5.2 Hz, 1H), 5.05-4.93 (m, 2H), 4.06 (dd, J =11.7, 7.5 Hz, 1H), 3.89 (s, 4H), 3.80-3.72 (m, 1H), 3.57 (dd, J = 13.5,2.9 Hz, 1H), 3.50 (dd, J = 10.8, 5.5 Hz, 1H), 3.45-3.37 (m, 1H), 3.36-3.25 (m, 2H), 2.82-2.71 (m, 1H), 2.39-2.23 (m, 2H), 2.15-1.87 (m, 3H),1.54 (d, J = 6.4 Hz, 3H) F7 116-120 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.94(s, — (m/z) 1H), 8.48 (d, J = 8.3 Hz, 1H), [M + H]⁺ 8.19 (dd, J = 8.4,1.4 Hz, 1H), calcd for 7.93 (d, J = 5.2 Hz, 1H), 7.84 C₃₁H₃₉N₂O₇, (dd, J= 7.9, 1.6 Hz, 1H), 7.73 551.2752; (d, J = 8.2 Hz, 1H), 7.55- found 7.43(m, 2H), 7.39 (dd, J = 551.2762 8.1, 6.9 Hz, 1H), 7.33 (dd, J = 7.0, 1.3Hz, 1H), 6.82 (d, J = 5.2 Hz, 1H), 5.04-4.93 (m, 2H), 4.06 (dd, J =11.7, 7.5 Hz, 1H), 3.90 (s, 3H), 3.87- 3.78 (m, 1H), 3.78-3.63 (m, 2H),3.56-3.37 (m, 2H), 3.37- 3.23 (m, 2H), 2.73 (app t, J = 12.8 Hz, 1H),2.14-2.01 (m, 1H), 1.80-1.66 (m, 2H), 1.56 (d, J = 6.4 Hz, 3H), 1.51-1.33 (m, 4H), 0.93 (t, J = 7.1 Hz, 3H) F8 94-98 — HRMS-ESI ¹H NMR(CDCl₃) δ 11.94 (s, — (m/z) 1H), 8.50 (d, J = 8.4 Hz, 1H), [M + H]⁺ 8.07(dd, J = 8.4, 1.3 Hz, 1H), calcd for 7.92 (d, J = 5.2 Hz, 1H), 7.85-C₃₃H₃₅N₂O₇, 7.77 (m, 1H), 7.70 (d, J = 571.2439; 8.1 Hz, 1H), 7.54-7.40(m, found 2H), 7.35 (dd, J = 8.1, 7.0 Hz, 571.2448 1H), 7.28 (dd, J =7.0, 1.3 Hz, 1H), 7.17-7.10 (m, 2H), 7.06- 6.99 (m, 2H), 6.80 (d, J =5.2 Hz, 1H), 5.22-5.10 (m, 1H), 5.06 (app q, J = 7.9 Hz, 1H), 4.44 (appt, J = 9.0 Hz, 1H), 4.14-4.04 (m, 1H), 3.88 (s, 3H), 3.64-3.47 (m, 3H),3.36 (dd, J = 11.7, 7.8 Hz, 1H), 2.69 (app t, J = 12.9 Hz, 1H),2.38-2.24 (m, 4H), 1.44 (d, J = 6.4 Hz, 3H) F9 78-85 — HRMS-ESI ¹H NMR(CDCl₃) δ 11.94 (s, — (m/z) 1H), 8.45 (d, J = 8.4 Hz, 1H), [M + H]⁺8.15-8.08 (m, 1H), 7.94 (d, J = calcd for 5.2 Hz, 1H), 7.84 (dd, J =C₃₁H₃₇N₂O₇, 8.1, 1.5 Hz, 1H), 7.73 (d, J = 549.2595; 8.1 Hz, 1H),7.56-7.44 (m, found 2H), 7.44-7.37 (m, 1H), 7.34 549.2599 (dd, J = 7.0,1.4 Hz, 1H), 6.83 (d, J = 5.2 Hz, 1H), 5.05- 4.90 (m, 2H), 4.29-4.19 (m,1H), 4.09 (dd, J = 11.6, 7.2 Hz, 1H), 3.91 (s, 3H), 3.75 (dd, J = 13.6,2.8 Hz, 1H), 3.57-3.43 (m, 2H), 3.43- 3.36 (m, 1H), 3.25 (dd, J = 11.7,7.9 Hz, 1H), 2.76 (app dd, J = 13.7, 12.0 Hz, 1H), 2.08-1.96 (m, 1H),1.93- 1.75 (m, 6H), 1.65-1.55 (m, 5H) F10 78-80 — HRMS-ESI ¹H NMR(CDCl₃) δ 11.94 (s, — (m/z) 1H), 8.48 (d, J = 8.4 Hz, 1H), [M + H]⁺8.23-8.15 (m, 1H), 7.95 (d, J = calcd for 5.2 Hz, 1H), 7.88-7.80 (m,C₃₀H₃₇N₂O₇, 1H), 7.73 (d, J = 8.1 Hz, 1H), 537.2595; 7.55-7.42 (m, 2H),7.40 (dd, found J = 8.1, 7.0 Hz, 1H), 7.33 (dd, 537.2594 J = 6.9, 1.3Hz, 1H), 6.83 (d, J = 5.2 Hz, 1H), 5.06-4.93 (m, 2H), 4.06 (dd, J =11.7, 7.5 Hz, 1H), 3.92 (s, 3H), 3.69 (dd, J = 13.7, 2.8 Hz, 1H), 3.60(dd, J = 8.4, 6.6 Hz, 1H), 3.56-3.41 (m, 3H), 3.38- 3.23 (m, 2H), 2.73(dd, J = 13.7, 11.9 Hz, 1H), 2.11 (ddq, J = 14.6, 8.7, 2.6 Hz, 1H), 2.01(p, J = 7.1, 6.7 Hz, 1H), 1.56 (d, J = 6.3 Hz, 3H), 1.05 (d, J = 2.3 Hz,3H), 1.03 (d, J = 2.2 Hz, 3H) F11 97-99 — HRMS-ESI ¹H NMR (CDCl₃) δ11.96 (s, — (m/z) 1H), 8.55 (d, J = 8.4 Hz, 1H), [M + H]⁺ 7.96 (d, J =5.2 Hz, 1H), 7.14- calcd for 7.04 (m, 4H), 6.84 (d, J = C₂₈H₃₉N₂O₇, 5.2Hz, 1H), 5.07-4.94 (m, 515.2752; 2H), 4.01 (dd, J = 11.7, 7.3 found, Hz,1H), 3.92 (s, 3H), 3.67 515.2766 (app dt, J = 8.6, 6.5 Hz, 1H),3.60-3.49 (m, 2H), 3.49- 3.38 (m, 2H), 3.19-3.07 (m, 2H), 2.34-2.23 (m,4H), 2.00- 1.87 (m, 1H), 1.67-1.55 (m, 2H), 1.51 (d, J = 6.3 Hz, 3H),1.42-1.28 (m, 4H), 0.96- 0.85 (m, 3H) F12 67-72 — HRMS-ESI ¹H NMR(CDCl₃) δ 11.93 (s, — (m/z) 1H), 8.56 (d, J = 8.3 Hz, 1H), [M + H]⁺ 7.96(d, J = 5.2 Hz, 1H), 7.09 calcd for (d, J = 7.7 Hz, 2H), 7.03 (d, J =C₂₇H₃₅N₂O₈, 8.0 Hz, 2H), 6.85 (d, J = 5.2 515.2388; Hz, 1H), 5.09 (m,2H), 4.97 found, (app t, J = 9.3 Hz, 1H), 4.02 515.2400 (dd, J = 11.7,7.3 Hz, 1H), 3.92 (s, 3H), 3.66-3.58 (m, 1H), 3.58-3.48 (m, 2H), 2.69(dd, J = 13.9, 3.6 Hz, 1H), 2.61 (app p, J = 7.0 Hz, 1H), 2.31 (s, 3H),2.24 (dd, J = 13.9, 11.4 Hz, 1H), 2.13- 2.04 (m, 1H), 1.35 (d, J = 6.3Hz, 3H), 1.22 (app dd, J = 7.0, 1.6 Hz, 6H) F13 68-73 — HRMS-ESI ¹H NMR(CDCl₃) δ 11.91 (s, — (m/z) 1H), 8.57 (d, J = 8.3 Hz, 1H), [M + H]⁺ 7.98(d, J = 5.2 Hz, 1H), 7.16- calcd for 7.07 (m, 2H), 7.04-6.93 C₂₆H₃₀N₂O₈,(m, 2H), 6.87 (d, J = 5.2 Hz, 517.1981; 1H), 5.17-5.01 (m, 2H), 4.97found (app t, J = 9.3 Hz, 1H), 4.04 517.2009 (dd, J = 11.7, 7.2 Hz, 1H),3.93 (s, 3H), 3.66-3.47 (m, 3H), 2.74 (dd, J = 14.2, 3.9 Hz, 1H), 2.29(app dd, J = 14.1, 11.1 Hz, 1H), 2.14- 2.01 (m, 1H), 1.70-1.59 (m, 1H),1.36 (d, J = 6.3 Hz, 3H), 1.08-1.00 (m, 2H), 0.96- 0.89 (m, 2H) F1466-71 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.91 (d, J = — (m/z) 0.6 Hz, 1H),8.56 (d, J = 8.3 [M + H]⁺ Hz, 1H), 7.98 (d, J = 5.2 Hz, calcd for 1H),7.15-7.06 (m, 2H), 7.03- C₂₆H₃₂FN₂O₈, 6.93 (m, 2H), 6.87 (d, J =519.2137; 5.2 Hz, 1H), 5.18-5.01 (m, found 2H), 4.98 (app t, J = 9.2 Hz,519.2160 1H), 4.05 (dd, J = 11.7, 7.2 Hz, 1H), 3.93 (s, 3H), 3.64- 3.48(m, 3H), 2.70 (dd, J = 14.1, 3.8 Hz, 1H), 2.61 (app p, J = 7.0 Hz, 1H),2.29 (dd, J = 14.1, 11.4 Hz, 1H), 2.11- 2.04 (m, 1H), 1.36 (d, J = 6.3Hz, 3H), 1.22 (app dd, J = 7.0, 1.8 Hz, 6H) F15 — — HRMS-ESI ¹H NMR(CDCl₃) δ 11.94 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.64 (d, J = 8.2 Hz,1H), 174.16, 170.80, [M]⁺ 8.01 (d, J = 5.2 Hz, 1H), 7.31- 168.94,155.36, calcd for 7.25 (m, 2H), 7.22-7.16 148.76, 141.69, C₂₇H₃₂N₂O₈,(m, 1H), 7.16-7.12 (m, 2H), 140.65, 130.20, 512.2159; 6.88 (d, J = 5.2Hz, 1H), 5.13- 128.41, 128.32, found 5.01 (m, 2H), 4.94 (t, J = 9.3125.95, 109.59, 76.27, 512.2158 Hz, 1H), 4.15-4.08 (m, 1H), 74.83,74.52, 73.04, 3.95 (s, 3H), 3.86 (dd, J = 56.10, 51.91, 43.86, 10.9, 1.5Hz, 1H), 3.80-3.62 32.49, 31.26, 18.30, (m, 3H), 2.77-2.67 (m, 1H),12.87, 8.58 2.54-2.43 (m, 1H), 1.90- 1.80 (m, 1H), 1.68-1.61 (m, 1H),1.57-1.48 (m, 1H), 1.34 (d, J = 6.3 Hz, 3H), 1.04- 0.98 (m, 2H),0.94-0.87 (m, 2H) F16 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.95 (s, ¹³C NMR(CDCl₃) δ (m/z) 1H), 8.65 (d, J = 8.3 Hz, 1H), 170.87, 168.96, [M]⁺ 8.01(d, J = 5.2 Hz, 1H), 7.25- 156.92, 155.36, calcd for 7.18 (m, 2H),7.18-7.11 148.75, 141.68, C₃₀H₃₄N₂O₇, (m, 1H), 7.10-7.05 (m, 2H),140.68, 130.55, 534.2366; 7.04-6.99 (m, 2H), 6.88 (d, J = 130.22,130.15, found, 5.2 Hz, 1H), 6.85-6.80 (m, 128.35, 128.31, 534.2377 2H),5.21-5.11 (m, 1H), 5.11- 125.83, 115.27, 5.02 (m, 1H), 4.26-4.12 109.60,81.88, 75.72, (m, 2H), 3.94 (s, 3H), 3.84- 74.57, 72.89, 56.10, 3.62 (m,3H), 2.72-2.63 (m, 51.83, 45.35, 33.10, 1H), 2.58-2.47 (m, 1H), 2.2931.19, 20.44, 19.04 (s, 3H), 1.98-1.81 (m, 2H), 1.62-1.50 (m, 1H), 1.38(d, J = 6.4 Hz, 3H) F17 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.92 (s, ¹³C NMR(CDCl₃) δ (m/z) 1H), 8.54 (d, J = 8.3 Hz, 1H), 171.04, 168.92, [M]⁺ 7.98(d, J = 5.2 Hz, 1H), 7.20- 161.47 (d, J = 244.4 calcd for 7.09 (m, 2H),7.07-6.94 Hz), 155.35, 148.73, C₂₆H₃₀F₄N₂O₇, (m, 2H), 6.86 (d, J = 5.2Hz, 140.64, 135.10 (d, J = 558.1989; 1H), 5.06-4.92 (m, 2H), 4.04 3.1Hz), 130.44 (d, J = found, (dd, J = 11.7, 7.2 Hz, 1H), 7.6 Hz), 130.15,558.2001 3.94 (s, 3H), 3.80-3.70 (m, 128.44, 115.33 (d, J = 1H),3.68-3.57 (m, 1H), 3.51- 21.2 Hz), 109.59, 3.40 (m, 3H), 3.18 (t, J =8.9 85.08, 75.41, 72.29, Hz, 1H), 3.02 (dd, J = 13.7, 72.18, 70.70,56.08, 3.6 Hz, 1H), 2.37 (dd, J = 51.50, 47.46, 34.42, 13.7, 11.6 Hz,1H), 2.29- 30.73 (q, J = 29.0 2.16 (m, 2H), 1.96-1.81 (m, Hz), 23.00 (q,J = 3H), 1.50 (d, J = 6.4 Hz, 3H) 2.7 Hz), 18.77 F18 — — HRMS-ESI ¹H NMR(CDCl₃) δ 11.95 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.53 (d, J = 8.3 Hz,1H), 171.17, 168.89, [M]⁺ 7.98 (d, J = 5.2 Hz, 1H), 7.19- 161.37 (d, J =243.8 calcd for 7.09 (m, 2H), 7.04-6.92 Hz), 155.33, 148.71,C₂₇H₃₃FN₂O₇, (m, 2H), 6.86 (d, J = 5.3 Hz, 140.61, 135.81 (d, J =516.2272; 1H), 5.08-4.97 (m, 1H), 4.93 3.1 Hz), 130.45 (d, J = found,(dt, J = 8.3, 7.2 Hz, 1H), 4.11- 7.9 Hz), 130.20, 516.2280 4.03 (m, 2H),3.93 (s, 3H), 115.24 (d, J = 21.2 3.49-3.42 (m, 2H), 3.40- Hz), 109.55,83.58, 3.29 (m, 2H), 3.15 (dd, J = 83.29, 76.27, 73.25, 13.8, 3.6 Hz,1H), 2.34 (dd, J = 72.52, 56.08, 51.77, 13.7, 12.2 Hz, 1H), 1.88- 47.73,34.34, 32.70, 1.54 (m, 7H), 1.60-1.49 (m, 32.62, 23.010, 23.006, 5H)18.89 F19 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.94 (s, ¹³C NMR (CDCl₃) δ(m/z) 1H), 8.55 (d, J = 8.4 Hz, 1H), 171.06, 168.91, [M]⁺ 8.02-7.95 (m,1H), 7.18- 161.41 (d, J = 244.0 calcd for 7.11 (m, 2H), 7.03-6.94 (m,Hz), 155.33, 148.72, C₂₇H₃₅FN₂O₇, 2H), 6.86 (d, J = 5.2 Hz, 1H), 140.63,135.48 (d, J = 518.2428; 5.06-4.95 (m, 2H), 4.03 (dd, 3.2 Hz), 130.50(d, J = found, J = 11.7, 7.3 Hz, 1H), 3.93 (s, 7.8 Hz), 130.18, 518.24313H), 3.72-3.61 (m, 1H), 3.59- 115.24 (d, J = 21.2 3.39 (m, 4H),3.19-3.07 Hz), 109.56, 84.92, (m, 2H), 2.33 (dd, J = 13.8, 75.84, 72.98,72.44, 11.8 Hz, 1H), 1.96-1.85 (m, 72.33, 56.08, 51.55, 1H), 1.67-1.55(m, 2H), 1.51 47.59, 34.38, 29.99, (d, J = 6.4 Hz, 3H), 1.41- 28.34,22.58, 18.75, 1.31 (m, 4H), 0.96-0.87 (m, 14.01 3H) F20 — — — ¹H NMR(CDCl₃) δ 11.92 (s, ¹³C NMR (CDCl₃) δ 1H), 8.56 (d, J = 8.3 Hz, 1H),171.12, 168.95, 7.99 (d, J = 5.2 Hz, 1H), 7.35- 161.44 (d, J = 244.27.28 (m, 2H), 7.12-7.06 Hz), 159.04, 155.37, (m, 2H), 7.01-6.91 (m, 5H),148.75, 140.67, 6.87 (d, J = 5.2 Hz, 1H), 5.25- 135.01, 130.48 (d, J =5.14 (m, 1H), 5.13-4.99 7.9 Hz), 130.14, (m, 1H), 4.33 (t, J = 8.9 Hz,129.79, 121.43, 1H), 4.14-4.07 (m, 1H), 3.94 115.41, 115.24 (d, J = (s,3H), 3.58 (d, J = 4.0 Hz, 20.8 Hz), 109.61, 2H), 3.49 (dd, J = 11.7, 7.381.76, 75.60, 72.26, Hz, 1H), 3.00 (dd, J = 13.8, 71.98, 56.10, 51.49,3.4 Hz, 1H), 2.33 (dd, J = 47.76, 34.54, 18.98 13.8, 11.6 Hz, 1H), 2.20-2.10 (m, 1H), 1.41 (d, J = 6.4 Hz, 3H) F21 — — HRMS-ESI ¹H NMR (CDCl₃) δ11.94 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.54 (d, J = 8.4 Hz, 1H), 171.08,168.91, [M]⁺ 7.98 (d, J = 5.2 Hz, 1H), 7.18- 161.42 (d, J = 244.3 calcdfor 7.11 (m, 2H), 7.01-6.95 Hz), 155.34, 148.72, C₂₆H₃₃FN₂O₇, (m, 2H),6.86 (d, J = 5.3 Hz, 140.63, 135.50 (d, J = 504.2272; 1H), 5.08-4.91 (m,2H), 4.04 3.1 Hz), 130.51 (d, J = found, (dd, J = 11.7, 7.3 Hz, 1H), 8.0Hz), 130.19, 504.2273 3.94 (s, 3H), 3.54-3.38 (m, 115.24 (d, J = 21.04H), 3.33 (dd, J = 8.3, 6.3 Hz, Hz), 109.56, 84.58, 1H), 3.19-3.06 (m,2H), 2.33 79.44, 77.21, 75.84, (dd, J = 13.8, 11.8 Hz, 1H), 72.29,56.09, 51.53, 1.90 (dq, J = 13.3, 6.8 Hz, 47.68, 34.29, 29.19, 2H), 1.51(d, J = 6.3 Hz, 3H), 19.48, 18.80 0.96 (d, J = 6.7 Hz, 6H) F22 — —HRMS-ESI ¹H NMR (CDCl₃) δ 11.92 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.56(d, J = 8.3 Hz, 1H), 174.28, 171.02, [M]⁺ 7.98 (d, J = 5.2 Hz, 1H),7.13- 168.89, 155.35, calcd for 7.08 (m, 2H), 7.08-7.01 148.74, 140.62,C₂₇H₃₂N₂O₈, (m, 2H), 6.86 (d, J = 5.2 Hz, 135.85, 135.82, 512.2159; 1H),5.15-5.02 (m, 2H), 4.97 130.16, 129.22, found, (t, J = 9.3 Hz, 1H), 4.01(dd, J = 128.90, 109.57, 76.93, 512.2157 11.7, 7.2 Hz, 1H), 3.93 (s,74.43, 73.00, 72.54, 3H), 3.68-3.62 (m, 1H), 3.58- 56.09, 51.71, 45.83,3.48 (m, 2H), 2.74 (dd, J = 34.51, 21.02, 18.26, 13.9, 3.7 Hz, 1H), 2.31(s, 12.87, 8.67, 8.65 3H), 2.28-2.19 (m, 1H), 2.16- 2.05 (m, 1H),1.69-1.60 (m, 1H), 1.36 (d, J = 6.3 Hz, 3H), 1.07-1.01 (m, 2H), 0.96-0.89 (m, 2H) F23 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.93 (s, ¹³C NMR (CDCl₃)δ (m/z) 1H), 8.53 (d, J = 8.3 Hz, 1H), 171.11, 168.90, [M]⁺ 7.98 (d, J =5.2 Hz, 1H), 7.09 155.33, 148.72, calcd for (q, J = 8.1 Hz, 4H), 6.86(d, J = 140.63, 136.33, C₂₇H₃₃F₃N₂O₇, 5.2 Hz, 1H), 5.05-4.95 (m, 135.77,130.17, 554.2240; 2H), 4.03 (dd, J = 11.7, 7.3 129.21, 128.94, found,Hz, 1H), 3.93 (s, 3H), 3.80- 127.09 (q, J = 276.1 554.2250 3.69 (m, 1H),3.68-3.56 (m, Hz), 109.57, 85.10, 1H), 3.55-3.49 (m, 1H), 3.49- 75.50,72.45, 72.18, 3.40 (m, 2H), 3.18 (t, J = 8.9 70.55, 56.08, 51.49, Hz,1H), 3.02 (dd, J = 13.6, 47.23, 34.78, 30.76 (q, 3.6 Hz, 1H), 2.39-2.28(m, J = 29.0 Hz), 22.99 4H), 2.27-2.16 (m, 2H), 2.01- (q, J = 3.1 Hz),21.01, 1.90 (m, 1H), 1.89-1.80 18.79 (m, 2H), 1.49 (d, J = 6.4 Hz, 3H)F24 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.93 ¹³C NMR (CDCl₃) δ (m/z) 1H),8.56 (d, J = 8.3 Hz, 1H), 171.17, 168.92, [M]⁺ 7.98 (d, J = 5.2 Hz, 1H),7.34- 159.15, 155.35, calcd for 7.27 (m, 2H), 7.11-6.93 148.74, 140.65,C₂₉H₃₂N₂O₇, (m, 7H), 6.86 (d, J = 5.2 Hz, 136.21, 135.68, 520.2226; 1H),5.25-5.14 (m, 1H), 5.05 130.16, 129.74, found, (q, J = 7.6 Hz, 1H), 4.33(t, J = 129.13, 128.98, 520.2210 8.9 Hz, 1H), 4.08 (dd, J = 121.33,115.48, 11.7, 7.3 Hz, 1H), 3.93 (s, 109.59, 81.89, 75.69, 3H), 3.79-3.56(m, 2H), 3.47 72.16, 56.09, 51.49, (dd, J = 11.7, 7.3 Hz, 1H), 47.59,34.82, 21.02, 3.01 (dd, J = 13.4, 3.0 Hz, 19.01 1H), 2.29 (m, 4H),2.23-2.11 (m, 1H), 1.41 (d, J = 6.4 Hz, 3H) F25 — — HRMS-ESI ¹H NMR(CDCl₃) δ 11.96 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.52 (d, J = 8.3 Hz,1H), 171.23, 168.87, [M]⁺ 7.98 (d, J = 5.2 Hz, 1H), 7.14- 155.32,148.71, calcd for 7.04 (m, 4H), 6.85 (d, J = 140.59, 137.07, C₂₈H₃₆N₂O₇,5.2 Hz, 1H), 5.02 (dq, J = 8.8, 135.53, 130.22, 512.2523; 6.5 Hz, 1H),4.97-4.88 (m, 129.16, 128.97, found, 1H), 4.11-4.01 (m, 2H), 3.93109.53, 83.56, 83.37, 512.2529 (s, 3H), 3.51-3.43 (m, 2H), 76.34, 73.51,72.38, 3.38-3.29 (m, 2H), 3.16 (dd, 56.07, 51.77, 47.49, J = 13.7, 3.6Hz, 1H), 2.33- 34.63, 32.71, 32.62, 2.25 (m, 4H), 1.92-1.62 (m, 23.03,23.00, 21.02, 7H), 1.61-1.49 (m, 5H) 18.90 F26 — — HRMS-ESI ¹H NMR(CDCl₃) δ 11.90 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.58 (d, J = 8.3 Hz,1H), 174.25, 170.94, [M]⁺ 7.99 (d, J = 5.2 Hz, 1H), 7.56 168.92, 155.35,calcd for (d, J = 8.1 Hz, 2H), 7.29 (d, J = 148.74, 143.29,C₂₇H₂₉F₃N₂O₈, 7.3 Hz, 2H), 6.87 (d, J = 5.2 140.65, 130.10, 566.1876;Hz, 1H), 5.18-4.96 (m, 3H), 129.31, 128.71 (q, J = found, 4.05 (dd, J =11.8, 7.2 Hz, 32.3 Hz), 125.45 (q, J = 566.1897 1H), 3.94 (s, 3H),3.67-3.50 3.8 Hz), 124.20 (q, J = (m, 3H), 2.82 (dd, J = 14.2, 271.8Hz), 109.61, 4.3 Hz, 1H), 2.43 (dd, J = 76.81, 74.26, 72.82, 14.2, 10.9Hz, 1H), 2.22- 72.62, 56.08, 51.66, 2.06 (m, 1H), 1.66-1.55 (m, 45.64,35.09, 18.19, 1H), 1.37 (d, J = 6.3 Hz, 3H), 12.77, 8.80, 8.71 1.08-0.99(m, 2H), 0.96- 0.88 (m, 2H) F27 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.93 (s,¹³C NMR (CDCl₃) δ (m/z) 1H), 8.55 (d, J = 8.3 Hz, 1H), 171.04, 168.93,[M]⁺ 7.98 (d, J = 5.2 Hz, 1H), 7.55 155.34, 148.72, calcd for (d, J =8.0 Hz, 2H), 7.32 (d, J = 144.20, 140.64, C₂₇H₃₃F₃N₂O₇, 7.9 Hz, 2H),6.86 (d, J = 5.2 130.16, 129.45, 554.224; Hz, 1H), 5.08-4.95 (m, 2H),128.52 (q, J = 32.5 found, 4.04 (dd, J = 11.7, 7.2 Hz, Hz), 125.39 (q, J= 554.2258 1H), 3.93 (s, 3H), 3.52-3.40 3.8 Hz), 124.28 (q, J = (m, 4H),3.34 (dd, J = 8.3, 6.4 271.6 Hz), 109.58, Hz, 1H), 3.25-3.11 (m, 2H),84.58, 79.56, 75.80, 2.50-2.37 (m, 1H), 2.02- 72.34, 72.26, 56.08, 1.93(m, 1H), 1.93-1.82 (m, 51.52, 47.48, 34.99, 1H), 1.51 (d, J = 6.3 Hz,3H), 29.18, 19.46, 18.80 0.96 (d, J = 6.7 Hz, 6H) F28 — — HRMS-ESI ¹HNMR (CDCl₃) δ 11.94 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.54 (d, J = 8.2Hz, 1H), 171.13, 168.92, [M]⁺ 7.98 (d, J = 5.2 Hz, 1H), 7.55 155.33,148.71, calcd for (d, J = 8.0 Hz, 2H), 7.32 (d, J = 144.53, 140.63,C₂₈H₃₃F₃N₂O₇, 8.0 Hz, 2H), 6.86 (d, J = 5.2 130.16, 129.40, 566.2240;Hz, 1H), 5.09-4.98 (m, 1H), 128.45 (q, J = 32.1 found, 4.94 (q, J = 7.4Hz, 1H), 4.16- Hz), 125.38 (q, J = 566.2241 4.04 (m, 2H), 3.93 (s, 3H),3.8 Hz), 124.29 (q, J = 3.50-3.31 (m, 4H), 3.23 (dd, 271.9 Hz), 109.58,J = 13.7, 3.5 Hz, 1H), 2.45 83.64, 83.25, 76.23, (dd, J = 13.7, 12.2 Hz,1H), 73.16, 72.59, 56.07, 1.96-1.66 (m, 7H), 1.63- 51.77, 47.48, 35.04,1.55 (m, 2H), 1.53 (d, J = 6.5 32.70, 32.62, 23.00, Hz, 3H) 18.89 F29 —— HRMS-ESI ¹H NMR (CDCl₃) δ 11.93 (s, ¹⁹F NMR (CDCl₃) (m/z) 1H), 8.56(d, J = 8.3 Hz, 1H), δ −62.35 [M]⁺ 7.98 (d, J = 5.2 Hz, 1H), 7.58- calcdfor 7.49 (m, 2H), 7.32 (d, J = C₂₆H₃₁F₃N₂O₇, 8.0 Hz, 2H), 6.86 (d, J =5.2 540.2083; Hz, 1H), 5.07-4.95 (m, 2H), found, 4.04 (dd, J = 11.7, 7.2Hz, 540.2101 1H), 3.93 (s, 3H), 3.66 (dt, J = 8.6, 6.6 Hz, 1H),3.57-3.39 (m, 4H), 3.23-3.13 (m, 2H), 2.43 (dd, J = 13.7, 11.7 Hz, 1H),2.03-1.91 (m, 1H), 1.70- 1.59 (m, 2H), 1.52 (d, J = 6.4 Hz, 3H), 0.97(t, J = 7.4 Hz, 3H) F30 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.90 (s, ¹⁹F NMR(CDCl₃) (m/z) 1H), 8.56 (d, J = 8.3 Hz, 1H), δ −62.43 [M]⁺ 7.99 (d, J =5.2 Hz, 1H), 7.56 calcd for (d, J = 8.0 Hz, 2H), 7.27 (d, J =C₂₇H₃₁F₃N₂O₈, 8.0 Hz, 2H), 6.87 (d, J = 5.2 568.2033; Hz, 1H), 5.19-4.96(m, 3H), found, 4.06 (dd, J = 11.8, 7.2 Hz, 568.2060 1H), 3.94 (s, 3H),3.58-3.49 (m, 3H), 2.77 (dd, J = 14.0, 3.9 Hz, 1H), 2.59 (hept, J = 7.0Hz, 1H), 2.41 (dd, J = 14.1, 11.4 Hz, 1H), 2.19- 2.07 (m, 1H), 1.36 (d,J = 6.3 Hz, 3H), 1.22 (app dd, J = 7.0, 2.9 Hz, 6H) F31 — — HRMS-ESI ¹HNMR (CDCl₃) δ 11.93 (s, ¹⁹F NMR (CDCl₃) (m/z) 1H), 8.55 (d, J = 8.3 Hz,1H), δ −62.34 [M]⁺ 7.98 (d, J = 5.2 Hz, 1H), 7.62- calcd for 7.52 (m,2H), 7.32 (d, J = C₂₈H₃₅F₃N₂O₇, 8.0 Hz, 2H), 6.86 (d, J = 5.2 568.2396;Hz, 1H), 5.06-4.96 (m, 2H), found, 4.04 (dd, J = 11.7, 7.2 Hz, 568.24251H), 3.93 (s, 3H), 3.73-3.65 (m, 1H), 3.59-3.51 (m, 1H), 3.51-3.39 (m,3H), 3.23- 3.13 (m, 2H), 2.43 (dd, J = 13.7, 11.7 Hz, 1H), 2.03- 1.90(m, 1H), 1.67-1.56 (m, 2H), 1.52 (d, J = 6.4 Hz, 3H), 1.41-1.29 (m, 4H),0.94- 0.87 (m, 3H) F32 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.91 (s, ¹³C NMR(CDCl₃) δ (m/z) 1H), 8.57 (d, J = 8.3 Hz, 1H), 171.00, 168.95, [M]⁺ 8.00(d, J = 5.2 Hz, 1H), 6.88 155.36, 148.74, calcd for (d, J = 5.2 Hz, 1H),5.09- 140.67, 130.15, C₂₁H₂₉F₃N₂O₇, 4.91 (m, 2H), 4.13 (dd, J = 127.00(q, J = 277.3 478.1927; 11.8, 7.3 Hz, 1H), 3.94 (s, Hz), 109.61, 83.19,found, 3H), 3.75-3.65 (m, 2H), 3.53 78.88, 75.68, 72.80, 478.1923 (dd, J= 11.8, 7.5 Hz, 1H), 72.22, 56.10, 51.39, 3.42 (dd, J = 8.4, 6.4 Hz,1H), 40.00, 32.61 (q, J = 3.21 (dd, J = 8.4, 6.4 Hz, 1H), 28.3 Hz),29.05, 3.12 (t, J = 8.8 Hz, 1H), 2.51- 19.30, 18.86 2.33 (m, 1H),2.25-2.11 (m, 1H), 2.11-2.00 (m, 1H), 1.92- 1.77 (m, 1H), 1.49 (d, J =6.5 Hz, 3H), 0.93 (d, J = 6.7 Hz, 6H) F33 — — HRMS-ESI ¹H NMR (CDCl₃) δ11.92 (s, ¹⁹F NMR (CDCl₃) (m/z) 1H), 8.56 (d, J = 8.3 Hz, 1H), δ −63.68[M]⁺ 8.00 (d, J = 5.2 Hz, 1H), 6.88 calcd for (d, J = 5.2 Hz, 1H), 5.04(dq, J = C₂₂H₂₉F₃N₂O₇, 8.2, 6.5 Hz, 1H), 4.93 (td, J = 490.1927; 8.1,6.7 Hz, 1H), 4.18 (dd, J = found, 11.7, 6.7 Hz, 1H), 4.04- 490.1929 3.90(m, 4H), 3.69 (qd, J = 11.8, 4.2 Hz, 2H), 3.47 (dd, J = 11.7, 8.0 Hz,1H), 3.28 (t, J = 7.8 Hz, 1H), 2.60-2.41 (m, 1H), 2.22-2.08 (m, 1H),2.03- 1.90 (m, 1H), 1.83-1.65 (m, 5H), 1.65-1.53 (m, 3H), 1.49 (d, J =6.5 Hz, 3H) F34 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.97 (s, ¹³C NMR (CDCl₃)δ (m/z) 1H), 8.63 (d, J = 8.2 Hz, 1H), 170.88, 168.91, [M]⁺ 7.99 (d, J =5.2 Hz, 1H), 6.87 155.30, 148.70, calcd for (d, J = 5.2 Hz, 1H), 5.08-140.62, 130.25, C₂₄H₃₈N₂O₇, 4.93 (m, 2H), 4.06 (dd, J = 109.54, 84.49,78.95, 466.2679; 11.8, 7.0 Hz, 1H), 3.94 (s, 75.98, 75.35, 72.89, found,3H), 3.72-3.62 (m, 2H), 3.52 56.07, 51.93, 45.81, 466.2685 (dd, J =10.8, 6.4 Hz, 1H), 36.05, 29.13, 28.38, 3.35 (dd, J = 8.3, 6.4 Hz, 1H),26.71, 22.76, 22.42, 3.27 (dd, J = 8.3, 6.3 Hz, 1H), 19.48, 18.89 3.03(t, J = 9.1 Hz, 1H), 1.84 (hept, J = 6.6 Hz, 1H), 1.73- 1.57 (m, 2H),1.57-1.49 (m, 1H), 1.46 (d, J = 6.4 Hz, 3H), 1.36-1.22 (m, 1H), 1.21-1.08 (m, 2H), 0.93 (d, J = 6.7 Hz, 6H), 0.89 (app dd, J = 6.6, 3.5 Hz,6H) F35 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.95 (s, ¹³C NMR (CDCl₃) δ (m/z)1H), 8.62 (d, J = 8.3 Hz, 1H), 170.88, 168.93, [M]⁺ 8.00 (d, J = 5.2 Hz,1H), 6.87 155.33, 148.72, calcd for (d, J = 5.2 Hz, 1H), 5.10- 140.65,130.21, C₂₄H₃₅F₃N₂O₇, 4.90 (m, 2H), 4.07 (dd, J = 127.12 (q, J = 276.0520.2396; 11.8, 7.1 Hz, 1H), 3.94 (s, Hz), 109.56, 84.96, found, 3H),3.70-3.60 (m, 3H), 3.60- 75.58, 74.93, 72.81, 520.2407 3.49 (m, 2H),3.07 (t, J = 8.9 70.28, 56.08, 51.84, Hz, 1H), 2.29-2.12 (m, 2H), 45.71,35.99, 30.77 (q, 1.89-1.77 (m, 2H), 1.68- J = 29.0 Hz), 28.33, 1.48 (m,3H), 1.46 (d, J = 6.4 26.85, 22.96 (q, J = Hz, 3H), 1.36-1.24 (m, 1H),3.1 Hz), 22.74, 22.33, 1.23-1.08 (m, 2H), 0.92- 18.90 0.86 (m, 6H) F36 —— HRMS-ESI ¹H NMR (CDCl₃) δ 11.94 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.65(d, J = 8.2 Hz, 1H), 174.11, 170.79, [M]⁺ 8.00 (d, J = 5.1 Hz, 1H), 6.88168.92, 155.33, calcd for (d, J = 5.3 Hz, 1H), 5.12- 148.73, 140.63,C₂₄H₃₄N₂O₈, 5.01 (m, 2H), 4.88 (t, J = 9.4 130.19, 109.57, 76.49,478.2315; Hz, 1H), 4.07 (dd, J = 11.8, 75.39, 74.56, 73.14, found, 7.0Hz, 1H), 3.94 (s, 3H), 3.81- 56.08, 52.02, 44.50, 478.2324 3.70 (m, 2H),3.59 (dd, J = 35.31, 28.19, 26.98, 10.8, 7.1 Hz, 1H), 1.80-1.69 22.69,22.17, 18.31, (m, 1H), 1.69-1.60 (m, 1H), 12.83, 8.41 1.52-1.41 (m, 1H),1.37- 1.31 (m, 4H), 1.29-0.99 (m, 5H), 0.95-0.89 (m, 2H), 0.89- 0.82 (m,6H) F37 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.95 (s, ¹³C NMR (CDCl₃) δ (m/z)1H), 8.65 (d, J = 8.3 Hz, 1H), 170.90, 168.95, [M]⁺ 8.00 (d, J = 5.1 Hz,1H), 7.14- 157.07, 155.34, calcd for 7.03 (m, 2H), 6.87 (d, J = 148.73,140.66, C₂₇H₃₆N₂O₇, 5.2 Hz, 1H), 6.85-6.77 (m, 130.38, 130.22, 500.2523;2H), 5.15 (dt, J = 8.9, 6.4 Hz, 130.06, 115.23, found, 1H), 5.06 (dt, J= 8.3, 6.8 Hz, 109.58, 82.05, 75.82, 500.2521 1H), 4.21-4.06 (m, 2H),3.94 74.82, 72.86, 56.09, (s, 3H), 3.79-3.59 (m, 3H), 51.87, 45.99,35.93, 2.29 (s, 3H), 1.87-1.77 (m, 28.04, 27.00, 22.79, 1H), 1.63-1.49(m, 1H), 1.37 22.13, 20.44, 19.09 (d, J = 6.4 Hz, 4H), 1.22- 1.07 (m,3H), 0.79 (d, J = 6.6 Hz, 3H), 0.75 (d, J = 6.5 Hz, 3H) F38 — — HRMS-ESI¹H NMR (CDCl₃) δ 11.97 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.64 (d, J = 8.3Hz, 1H), 170.88, 168.91, [M]⁺ 7.99 (d, J = 5.2 Hz, 1H), 6.87 155.30,148.69, calcd for (d, J = 5.2 Hz, 1H), 5.08- 140.63, 130.23, C₂₃H₃₆N₂O₇,4.91 (m, 2H), 4.06 (dd, J = 109.54, 84.76, 75.99, 452.2523; 11.8, 7.0Hz, 1H), 3.94 (s, 75.32, 74.08, 72.88, found, 3H), 3.73-3.63 (m, 2H),3.59- 56.07, 51.91, 45.79, 452.2516 3.41 (m, 3H), 3.04 (t, J = 9.136.01, 28.35, 26.79, Hz, 1H), 1.71-1.50 (m, 5H), 23.43, 22.78, 22.37,1.47 (d, J = 6.4 Hz, 3H), 1.34- 18.85, 10.70 1.24 (m, 1H), 1.23-1.09 (m,2H), 0.94 (t, J = 7.4 Hz, 3H), 0.89 (app dd, J = 6.6, 4.0 Hz, 6H) F39 —— HRMS-ESI ¹H NMR (CDCl₃) δ 11.98 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 0.6Hz, 1H), 8.63 (d, J = 8.2 170.91, 168.90, [M]⁺ Hz, 1H), 7.99 (d, J = 5.2Hz, 155.30, 148.69, calcd for 1H), 6.87 (dd, J = 5.3, 0.6 Hz, 140.60,130.27, C₂₅H₃₈N₂O₇, 1H), 5.07-4.90 (m, 2H), 4.16- 109.52, 83.55, 83.23,478.2679; 4.04 (m, 1H), 4.02-3.96 76.61, 76.32, 73.36, found, (m, 1H),3.94 (s, 3H), 3.69- 56.06, 52.25, 46.20, 478.2686 3.59 (m, 2H), 3.55(dd, J = 36.70, 32.59, 32.53, 11.4, 6.3 Hz, 1H), 3.19 (t, J = 28.43,26.81, 23.06, 8.5 Hz, 1H), 1.79-1.60 (m, 23.02, 22.73, 22.49, 7H),1.59-1.50 (m, 4H), 1.47 18.94 (d, J = 6.4 Hz, 3H), 1.36- 1.27 (m, 1H),1.20-1.04 (m, 2H), 0.89 (app dd, J = 6.6, 4.4 Hz, 6H) F40 — — HRMS-ESI¹H NMR (CDCl₃) δ 11.92 (s, ¹⁹F NMR (CDCl₃) (m/z) 1H), 8.55 (d, J = 8.3Hz, 1H), δ −134.7 (dd, [M]⁺ 7.99 (d, J = 5.2 Hz, 1H), 6.90- J = 20.4,8.1 calcd for 6.77 (m, 3H), 5.08-4.93 Hz), −163.8-−164.1 C₂₆H₃₁F₃N₂O₇,(m, 2H), 4.06 (dd, J = 11.8, (m) 540.2083; 7.2 Hz, 1H), 3.94 (s, 3H),3.52- found, 3.41 (m, 4H), 3.30 (dd, J = 540.2091 8.4, 6.3 Hz, 1H),3.17-3.00 (m, 2H), 2.33 (dd, J = 13.8, 11.8 Hz, 1H), 1.94-1.80 (m, 2H),1.50 (d, J = 6.4 Hz, 3H), 0.96 (app dd, J = 6.7, 1.4 Hz, 6H) F41 79-82 —HRMS-ESI ¹H NMR (CDCl₃) δ 11.91 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.54(d, J = 8.3 Hz, 1H), 176.29, 171.06, [M]⁺ 7.98 (d, J = 5.2 Hz, 1H), 7.36168.93, 155.36, calcd for (s, 1H), 7.20-7.13 (m, 2H), 148.75, 140.64,C₂₆H₃₀Cl₂N₂O₈, 6.87 (d, J = 5.2 Hz, 1H), 5.18- 135.15, 134.89, 568.1379;4.96 (m, 3H), 4.10 (dd, J = 132.98, 132.37, found, 11.7, 7.3 Hz, 1H),3.94 (s, 130.10, 129.51, 568.1385 3H), 3.59-3.43 (m, 3H), 2.81 127.14,109.61, 76.52, (dd, J = 13.9, 3.6 Hz, 1H), 74.17, 72.27, 71.61, 2.62 (p,J = 7.0 Hz, 1H), 2.60- 56.09, 51.46, 43.98, 2.56 (m, 1H), 2.16 (bs, 1H),34.22, 32.31, 19.04, 1.36 (d, J = 6.3 Hz, 3H), 1.23 18.97, 18.16. (d, J= 7.0 Hz, 6H) F42 60-64 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.94 (s, ¹³C NMR(CDCl₃) δ (m/z) 1H), 8.56 (d, J = 8.1 Hz, 1H), 171.01, 168.91, [M]⁺ 7.98(d, J = 5.2 Hz, 1H), 7.36 155.32, 148.71, calcd for (s, 1H), 7.26-7.10(m, 2H), 140.63, 136.12, C₂₆H₃₂Cl₂N₂O₇, 6.86 (d, J = 5.3 Hz, 1H), 5.09-135.03, 132.57, 554.1585; 4.95 (m, 2H), 4.06 (dd, J = 132.13, 130.15,found, 11.7, 7.2 Hz, 1H), 3.93 (s, 129.35, 127.09, 554.1584 3H),3.51-3.40 (m, 4H), 3.36 109.57, 84.92, 79.81, (dd, J = 8.3, 6.5 Hz, 1H),3.23- 75.84, 72.36, 60.38, 3.08 (m, 2H), 2.62-2.46 56.07, 51.57, 45.89,(m, 1H), 2.10-1.98 (m, 1H), 32.10, 29.16, 19.48, 1.88 (dq, J = 13.2, 6.6Hz, 18.75 1H), 1.51 (d, J = 6.4 Hz, 3H), 0.95 (d, J = 7.5 Hz, 6H) F4350-54 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.94 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H),8.55 (d, J = 8.2 Hz, 1H), 171.03, 168.92, [M]⁺ 7.98 (d, J = 5.2 Hz, 1H),7.36 155.33, 148.71, calcd for (s, 1H), 7.24-7.11 (m, 2H), 140.64,136.10, C₂₇H₃₄Cl₂N₂O₇ 6.86 (d, J = 5.2 Hz, 1H), 5.09- 135.03, 132.59,568.1743; 4.92 (m, 2H), 4.06 (dd, J = 132.11, 130.16, found, 11.7, 7.2Hz, 1H), 3.93 (s, 129.37, 127.09, 568.1763 3H), 3.74-3.63 (m, 1H), 3.57109.57, 85.20, 75.84, (q, J = 8.4, 7.5 Hz, 1H), 3.50- 73.35, 72.34,72.19, 3.37 (m, 3H), 3.24-3.08 (m, 56.08, 51.54, 45.87, 2H), 2.62-2.48(m, 1H), 2.07- 32.17, 29.97, 28.33, 1.98 (m, 1H), 1.64-1.55 22.58,18.72, 14.02 (m, 2H), 1.51 (d, J = 6.4 Hz, 3H), 1.39-1.28 (m, 4H), 0.90(t, J = 7.1 Hz, 3H) F44 81-85 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.94 (s, ¹³CNMR (CDCl₃) δ (m/z) 1H), 8.57 (d, J = 8.3 Hz, 1H), 171.12, 168.97, [M]⁺7.97 (d, J = 5.2 Hz, 1H), 7.32 156.95, 155.35, calcd for (s, 1H), 7.15(s, 2H), 7.10 (d, J = 148.74, 140.67, C₂₉H₃₀Cl₂N₂O₇, 8.3 Hz, 2H),6.91-6.83 (m, 135.75, 134.96, 588.1430; 3H), 5.26-5.13 (m, 1H), 5.06132.70, 132.22, found, (q, J = 7.5 Hz, 1H), 4.31 (t, J = 130.69, 130.20,588.1425 8.8 Hz, 1H), 4.20-4.04 (m, 129.38, 127.05, 1H), 3.92 (s, 3H),3.65-3.37 115.16, 109.63, 81.93, (m, 3H), 3.05 (dd, J = 13.7, 77.32,75.60, 72.16, 3.5 Hz, 1H), 2.61-2.45 (m, 71.59, 56.09, 51.45, 1H), 2.29(s, 3H), 2.28-2.21 46.08, 32.40, 20.45, (m, 1H), 1.42 (d, J = 6.5 Hz,18.93 3H) F45 55-59 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.94 (s, ¹³C NMR(CDCl₃) δ (m/z) 1H), 8.61 (d, J = 8.2 Hz, 1H), 176.19, 171.00, [M]⁺ 8.00(d, J = 5.2 Hz, 1H), 6.88 168.92, 155.35, calcd for (d, J = 5.1 Hz, 1H),5.11- 148.75, 140.63, C₂₅H₃₆N₂O₈, 5.01 (m, 2H), 4.81 (t, J = 9.2 130.19,109.58, 74.52, 492.2472; Hz, 1H), 4.10 (dd, J = 11.8, 74.16, 72.60,56.09, found, 7.2 Hz, 1H), 3.94 (s, 3H), 3.77- 51.75, 43.55, 37.20,492.2488 3.59 (m, 3H), 2.59 (hept, J = 35.00, 34.26, 33.62, 7.0 Hz, 1H),1.90-0.95 32.13, 25.02, 19.03, (m, 12H), 1.32 (d, J = 6.4 Hz, 18.32 3H),1.20 (d, J = 7.0 Hz, 6H) F46 132-134 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.97(s, ¹³C NMR (CDCl₃) δ (m/z) 1H), 8.61 (d, J = 8.2 Hz, 1H), 171.04,168.91, [M]⁺ 7.99 (d, J = 5.2 Hz, 1H), 6.87 155.31, 148.70, calcd for(d, J = 5.2 Hz, 1H), 5.11- 140.61, 130.25, C₂₅H₃₈N₂O₇, 4.85 (m, 2H),4.09 (dd, J = 109.54, 84.92, 79.14, 478.2679; 11.7, 7.1 Hz, 1H), 3.94(s, 76.03, 74.47, 72.53, found, 3H), 3.71-3.47 (m, 3H), 3.37 56.06,51.75, 44.72, 478.2673 (dd, J = 8.3, 6.3 Hz, 1H), 3.25 37.39, 34.94,33.86, (dd, J = 8.2, 6.7 Hz, 1H), 2.98 32.01, 29.13, 25.05, (t, J = 8.9Hz, 1H), 1.95-1.49 19.51, 18.83 (m, 10H), 1.46 (d, J = 6.4 Hz, 3H),1.31-1.21 (m, 1H), 1.15- 1.05 (m, 2H), 0.92 (dd, J = 6.7, 4.3 Hz, 6H)F47 109-111 — HRMS-ESI ¹H NMR (CDCl₃) δ 11.97 (s, ¹³C NMR (CDCl₃) δ(m/z) 1H), 8.61 (d, J = 8.3 Hz, 1H), 171.05, 168.91, [M]⁺ 7.99 (d, J =5.2 Hz, 1H), 6.87 155.32, 148.71, calcd for (d, J = 5.2 Hz, 1H), 5.09-140.62, 130.25, C₂₆H₄₀N₂O₇, 4.85 (m, 2H), 4.08 (dd, J = 109.54, 85.26,76.03, 492.2836; 11.7, 7.1 Hz, 1H), 3.94 (s, 74.51, 72.55, 56.07, found,3H), 3.74-3.35 (m, 5H), 2.99 51.75, 44.71, 37.40, 492.2840 (t, J = 9.0Hz, 1H), 1.96-1.83 35.09, 33.85, 32.05, (m, 1H), 1.83-1.71 (m, 2H),29.95, 28.37, 25.10, 1.72-1.48 (m, 8H), 1.47 (d, J = 22.56, 18.80, 14.006.4 Hz, 3H), 1.38-1.22 (m, 5H), 1.17-1.02 (m, 2H), 0.94- 0.86 (m, 3H)F48 — — HRMS-ESI ¹H NMR (CDCl₃) δ 11.95 (s, ¹³C NMR (CDCl₃) δ (m/z) 1H),8.54 (d, J = 8.3 Hz, 1H), 171.15, 168.90, [M + H]⁺ 7.97 (d, J = 5.2 Hz,1H), 7.09 155.31, 148.71, calcd for (d, J = 2.1 Hz, 4H), 6.85 (d, J =140.62, 136.76, C₂₇H₃₇N₂O₇, 5.2 Hz, 1H), 5.01 (m, 2H), 135.58, 130.20,501.2595; 3.92 (s, 3H), 4.02 (dd, J = 129.15, 129.05, found, 11.7, 7.3Hz, 1H), 3.49 (d, J = 109.56, 84.61, 79.28, 501.2602 7.7 Hz, 1H), 3.44(m, 3H), 75.92, 72.53, 72.16, 3.34 (dd, J = 8.3, 6.5 Hz, 1H), 56.08,51.53, 47.47, 3.13 (m, 2H), 2.31 (s, 4H), 34.60, 29.20, 21.03, 1.89 (dt,J = 13.2, 6.6 Hz, 2H), 19.50, 18.83 1.50 (d, J = 6.4 Hz, 3H), 0.96 (d, J= 6.7 Hz, 6H) F49 59-64 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.65 (d, J = — (m/z)8.7 Hz, 1H), 8.34 (d, J = 5.4 [M + H]⁺ Hz, 1H), 7.33-7.24 (m, 2H), calcdfor 7.24-7.13 (m, 3H), 7.01 (d, J = C₂₉H₃₆F₃N₂O₈, 5.4 Hz, 1H), 5.07-4.88(m, 597.2418, 2H), 4.08 (dd, J = 11.7, 7.1 found, Hz, 1H), 3.90 (s, 3H),3.71 597.2446 (dd, J = 10.9, 1.7 Hz, 1H), 3.67-3.42 (m, 4H), 3.08 (appt, J = 8.9 Hz, 1H), 2.78 (ddd, J = 14.5, 10.3, 4.8 Hz, 1H), 2.55 (ddd, J= 13.7, 9.9, 6.8 Hz, 1H), 2.39 (s, 3H), 2.23-2.05 (m, 2H), 1.93-1.82 (m,1H), 1.81-1.74 (m, 2H), 1.73- 1.65 (m, 1H), 1.60-1.45 (m, 1H), 1.42 (d,J = 6.4 Hz, 3H) F50 61-65 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.66 (d, J = —(m/z) 7.9 Hz, 1H), 8.33 (d, J = 5.4 [M + H]⁺ Hz, 1H), 7.33-7.23 (m, 2H),calcd for 7.23-7.14 (m, 3H), 7.00 (d, J = C₂₉H₃₉N₂O₈, 5.4 Hz, 1H),5.08-4.91 (m, 543.2701, 2H), 4.07 (dd, J = 11.7, 7.1 found, Hz, 1H),3.89 (s, 3H), 3.73 543.2714 (dd, J = 11.0, 1.6 Hz, 1H), 3.65-3.55 (m,2H), 3.33- 3.18 (m, 2H), 3.06 (app t, J = 9.0 Hz, 1H), 2.76 (ddd, J =13.7, 10.9, 4.7 Hz, 1H), 2.56 (ddd, J = 13.7, 10.3, 6.4 Hz, 1H), 2.39(s, 3H), 1.96 (dddd, J = 13.7, 10.9, 6.6, 3.0 Hz, 1H), 1.88-1.65 (m,2H), 1.56- 1.41 (m, 4H), 0.89 (app dd, J = 6.7, 0.7 Hz, 6H) F51 104-108— HRMS-ESI ¹H NMR (CDCl₃) δ 8.53 (d, J = — (m/z) 8.2 Hz, 1H), 8.27 (d, J= 5.4 [M + H]⁺ Hz, 1H), 8.01-7.94 (m, 1H), calcd for 7.88-7.81 (m, 1H),7.73 (d, J = C₃₂H₃₇N₂O₉, 8.2 Hz, 1H), 7.55-7.43 (m, 593.2494; 2H), 7.39(dd, J = 8.2, 7.0 Hz, found, 1H), 7.29 (dd, J = 7.0, 1.2 Hz, 593.25021H), 6.96 (d, J = 5.4 Hz, 1H), 5.18-5.02 (m, 3H), 4.00 (dd, J = 11.7,7.4 Hz, 1H), 3.86 (s, 3H), 3.58 (d, J = 4.2 Hz, 2H), 3.37 (dd, J = 11.7,7.2 Hz, 1H), 3.22 (dd, J = 14.1, 3.1 Hz, 1H), 2.76-2.63 (m, 2H), 2.38(s, 3H), 2.34-2.22 (m, 1H), 1.38 (d, J = 5.7 Hz, 3H), 1.28 (app dd, J =7.0, 3.7 Hz, 6H) F52 85-91 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.51 (d, J = —(m/z) 8.5 Hz, 1H), 8.28 (d, J = 5.4 [M + H]⁺ Hz, 1H), 8.19 (dd, J = 8.6,1.4 calcd for Hz, 1H), 7.87-7.80 (m, 1H), C₃₃H₄₁N₂O₈, 7.72 (d, J = 8.1Hz, 1H), 7.55- 593.2857; 7.42 (m, 2H), 7.39 (dd, J = found, 8.1, 7.0 Hz,1H), 7.32 (dd, J = 593.2867 6.9, 1.3 Hz, 1H), 6.96 (d, J = 5.4 Hz, 1H),5.06-4.88 (m, 2H), 4.03 (dd, J = 11.7, 7.6 Hz, 1H), 3.91-3.77 (m, 4H),3.77-3.62 (m, 2H), 3.57- 3.38 (m, 2H), 3.32-3.20 (m, 2H), 2.76-2.65 (m,1H), 2.38 (s, 3H), 2.11-2.04 (m, 1H), 1.79-1.67 (m, 2H), 1.54 (d, J =6.4 Hz, 3H), 1.51-1.32 (m, 4H), 0.92 (t, J = 7.1 Hz, 3H) F53 — —HRMS-ESI ¹H NMR (CDCl₃) δ 8.56 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.4 Hz,1H), 8.31 (d, J = 5.4 171.66, 168.83, [M + H]⁺ Hz, 1H), 7.14-7.04 (m,4H), 162.65, 159.40, calcd for 6.98 (d, J = 5.5 Hz, 1H), 5.05- 146.75,141.13, C₃₀H₄₁N₂O₈, 4.91 (m, 2H), 3.97 (dd, J = 137.49, 136.78,557.2857; 11.7, 7.3 Hz, 1H), 3.88 (s, 135.54, 129.12, found, 3H),3.72-3.61 (m, 1H), 3.59- 129.11, 129.04, 557.286 3.46 (m, 2H), 3.46-3.34109.91, 84.93, 75.71, (m, 2H), 3.17-3.05 (m, 2H), 72.67, 72.37, 56.29,2.38 (s, 3H), 2.31 (s, 3H), 2.28- 51.61, 47.32, 34.72, 2.23 (m, 1H),1.99-1.86 30.01, 28.36, 22.59, (m, 1H), 1.66-1.55 (m, 2H), 21.02, 20.72,18.80, 1.49 (d, J = 6.3 Hz, 3H), 1.41- 14.03. 1.28 (m, 4H), 0.94-0.86(m, 3H) F54 88-93 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.58 (d, J = — (m/z) 8.3Hz, 1H), 8.32 (d, J = 5.4 [M + H]⁺ Hz, 1H), 7.13-7.06 (m, 2H), calcd for7.06-6.96 (m, 3H), 5.13- C₂₉H₃₇N₂O₉, 5.00 (m, 2H), 4.95 (app t, J =557.2494; 9.3 Hz, 1H), 3.98 (dd, J = found, 11.7, 7.3 Hz, 1H), 3.89 (s,557.2497 3H), 3.60 (dd, J = 10.8, 1.7 Hz, 1H), 3.55-3.41 (m, 2H), 2.67(dd, J = 13.8, 3.5 Hz, 1H), 2.64-2.52 (m, 1H), 2.38 (s, 3H), 2.31 (s,3H), 2.22 (dd, J = 13.7, 11.6 Hz, 1H), 2.14- 2.01 (m, 1H), 1.33 (d, J =6.3 Hz, 3H), 1.21 (app dd, J = 7.0, 1.6 Hz, 6H) F55 — — HRMS-ESI ¹H NMR(CDCl₃) δ 8.67 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.2 Hz, 1H), 8.33 (d, J =5.4 171.41, 168.84, [M + Na]⁺ Hz, 1H), 7.33-7.24 (m, 2H), 162.72,159.42, calc for 7.23-7.14 (m, 3H), 6.99 (d, J = 146.79, 142.18,C₃₀H₄₀N₂O₈Na, 5.5 Hz, 1H), 5.08-4.90 (m, 141.15, 137.52, 579.2677; 2H),4.07 (dd, J = 11.7, 7.1 128.39, 128.36, found, Hz, 1H), 3.88 (s, 3H),3.74 125.84, 109.95, 84.68, 579.2684 (dd, J = 10.9, 1.6 Hz, 1H), 75.68,74.69, 73.08, 3.65-3.55 (m, 2H), 3.55- 72.27, 56.30, 51.95, 3.39 (m,2H), 3.06 (app t, J = 45.18, 33.30, 31.11, 9.1 Hz, 1H), 2.76 (ddd, J =29.97, 28.37, 22.59, 13.7, 10.9, 4.7 Hz, 1H), 2.56 20.74, 18.85, 14.03(ddd, J = 13.8, 10.4, 6.3 Hz, 1H), 2.39 (s, 3H), 2.02-1.89 (m, 1H),1.76-1.64 (m, 1H), 1.59-1.41 (m, 6H), 1.37- 1.24 (m, 4H), 0.93-0.84 (m,3H) F56 74-79 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.59 (d, J = — (m/z) 8.1 Hz,1H), 8.32 (d, J = 5.4 [M + H]⁺ Hz, 1H), 7.14-7.05 (m, 2H), calcd for7.03-6.93 (m, 3H), 5.14- C₂₈H₃₄FN₂O₉, 5.01 (m, 2H), 4.95 (app t, J =561.2243; 9.3 Hz, 1H), 4.01 (dd, J = found, 11.7, 7.3 Hz, 1H), 3.89 (s,561.2263 3H), 3.61-3.43 (m, 3H), 2.68 (dd, J = 14.0, 3.8 Hz, 1H),2.64-2.52 (m, 1H), 2.38 (s, 3H), 2.27 (dd, J = 14.1, 11.3 Hz, 1H),2.11-1.98 (m, 1H), 1.33 (d, J = 6.3 Hz, 3H), 1.22 (app dd, J = 7.0, 1.8Hz, 6H) F57 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.67 (d, J = ¹³C NMR (CDCl₃) δ(m/z) 8.4 Hz, 1H), 8.34 (d, J = 5.4 174.16, 171.34, [M]⁺ Hz, 1H),7.30-7.25 (m, 2H), 168.86, 162.71, calcd for 7.21-7.11 (m, 3H), 7.01 (d,J = 159.45, 146.76, C₂₉H₃₄N₂O₉, 5.5 Hz, 1H), 5.13-5.05 (m, 141.76,141.11, 554.2264; 1H), 5.05-4.97 (m, 1H), 4.92 137.56, 128.39, found,(t, J = 9.3 Hz, 1H), 4.08 (dd, J = 128.32, 125.92, 554.2267 11.8, 7.2Hz, 1H), 3.91 (s, 109.95, 76.26, 74.46, 3H), 3.83 (dd, J = 10.9, 1.574.34, 73.14, 56.31, Hz, 1H), 3.72-3.62 (m, 2H), 51.94, 43.87, 32.45,2.77-2.66 (m, 1H), 2.53- 31.32, 20.73, 18.30, 2.42 (m, 1H), 2.40 (s,3H), 12.88, 8.55 1.89-1.79 (m, 1H), 1.68- 1.57 (m, 2H), 1.57-1.44 (m,1H), 1.32 (d, J = 6.3 Hz, 3H), 1.04-0.96 (m, 2H), 0.93- 0.85 (m, 2H) F58— — HRMS-ESI ¹H NMR (CDCl₃) δ 8.67 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.3Hz, 1H), 8.35 (d, J = 5.5 171.39, 168.87, [M]⁺ Hz, 1H), 7.24-7.18 (m,2H), 162.73, 159.44, calcd for 7.18-7.10 (m, 1H), 7.09- 156.97, 146.79,C₃₂H₃₆N₂O₈, 7.05 (m, 2H), 7.03-6.98 (m, 141.76, 141.14, 576.2472; 3H),6.85-6.79 (m, 2H), 5.17- 137.55, 130.48, found, 5.03 (m, 2H), 4.19 (t, J= 8.9 130.13, 128.35, 576.2492 Hz, 1H), 4.12 (dd, J = 11.7, 128.29,125.80, 7.2 Hz, 1H), 3.91 (s, 3H), 3.80 115.27, 109.95, 81.87, (dd, J =10.9, 1.7 Hz, 1H), 75.55, 74.33, 73.05, 3.72 (dd, J = 10.9, 6.5 Hz,56.31, 51.91, 45.40, 1H), 3.62 (dd, J = 11.7, 6.7 33.08, 31.25, 20.74,Hz, 1H), 2.72-2.61 (m, 1H), 20.43, 19.06 2.57-2.46 (m, 1H), 2.40 (s,3H), 2.28 (s, 3H), 1.97-1.80 (m, 2H), 1.60-1.47 (m, 1H), 1.36 (d, J =6.4 Hz, 3H) F59 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.59 (d, J = ¹³C NMR(CDCl₃) δ (m/z) 8.5 Hz, 1H), 8.33 (d, J = 5.5 171.64, 168.85, [M]⁺ Hz,1H), 7.36-7.28 (m, 2H), 162.71, 161.42 (d, J = calcd for 7.15-7.04 (m,2H), 7.04- 244.2 Hz), 159.44, C₃₀H₃₁FN₂O₈, 6.87 (m, 6H), 5.22-5.12 (m,159.08, 146.77, 566.2064; 1H), 5.05 (dt, J = 8.6, 7.4 Hz, 141.07,137.55, found, 1H), 4.30 (t, J = 8.9 Hz, 1H), 135.07, 130.49 (d, J =566.2073 4.10-4.03 (m, 1H), 3.90 (s, 7.8 Hz), 129.77, 3H), 3.55 (d, J =4.1 Hz, 2H), 121.37, 115.42, 3.43 (dd, J = 11.7, 7.4 Hz, 115.20 (d, J =21.2 1H), 2.98 (dd, J = 13.8, 3.3 Hz), 109.96, 81.77, Hz, 1H), 2.39 (s,3H), 2.31 75.41, 72.42, 71.74, (dd, J = 13.8, 11.6 Hz, 1H), 56.31,51.57, 47.76, 2.19-2.07 (m, 1H), 1.38 (d, J = 34.57, 20.73, 18.99 6.4Hz, 3H) F60 — — ESIMS ¹H NMR (CDCl₃) δ 8.56 (d, J = ¹⁹F NMR (CDCl₃) m/z546 8.5 Hz, 1H), 8.32 (d, J = 5.4 δ −117.24 [M⁺] Hz, 1H), 7.20-7.09 (m,2H), 7.03-6.93 (m, 3H), 4.99 (ddd, J = 9.0, 7.9, 6.8 Hz, 2H), 4.00 (dd,J = 11.7, 7.3 Hz, 1H), 3.90 (s, 3H), 3.50-3.28 (m, 5H), 3.20-3.02 (m,2H), 2.38 (s, 3H), 2.30 (dd, J = 13.7, 11.7 Hz, 1H), 1.88 (ddt, J =13.3, 8.6, 4.8 Hz, 2H), 1.48 (d, J = 6.4 Hz, 3H), 0.96 (d, J = 6.7 Hz,6H) F61 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.59 (d, J = ¹³C NMR (CDCl₃) δ(m/z) 8.4 Hz, 1 H), 8.32 (d, J = 5.4 174.28, 171.55, [M]⁺ Hz, 1H),7.14-6.96 (m, 5H), 168.85, 162.65, calcd for 5.12-5.01 (m, 2H), 4.94 (t,J = 159.43, 146.72, C₂₉H₃₄N₂O₉, 9.3 Hz, 1H), 3.97 (dd, J = 141.09,137.54, 554.2264; 11.7, 7.3 Hz, 1H), 3.90 (s, 135.88, 135.80, found,3H), 3.65-3.57 (m, 1H), 3.54- 129.20, 128.90, 554.2270 3.43 (m, 2H),2.72 (dd, J = 109.91, 76.96, 74.25, 14.0, 3.7 Hz, 1H), 2.38 (s, 72.66,56.29, 51.73, 3H), 2.31 (s, 3H), 2.26-2.18 45.83, 34.56, 21.02, (m, 1H),2.14-2.04 (m, 1H), 20.72, 18.26, 12.88, 1.69-1.61 (m, 1H), 1.34 (d, J =8.64, 8.61 6.3 Hz, 3H), 1.07-1.01 (m, 2H), 0.97-0.86 (m, 2H) F62 — —HRMS-ESI ¹H NMR (CDCl₃) δ 8.56 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.5 Hz,1H), 8.32 (d, J = 5.5 171.65, 168.84, [M]⁺ Hz, 1H), 7.15-7.04 (m, 4H),162.66, 159.42, calcd for 6.99 (d, J = 5.5 Hz, 1H), 146.74, 141.10,C₂₉H₃₅F₃N₂O₈, 5.04-4.91 (m, 2H), 3.99 (dd, J = 137.51, 136.40, 596.2346;11.7, 7.4 Hz, 1H), 3.89 (s, 135.72, 129.18, found, 3H), 3.79-3.65 (m,1H), 3.63- 128.95, 127.11 596.2353 3.54 (m, 1H), 3.52-3.32 (q, J = 276.0Hz), (m, 3H), 3.16 (t, J = 9.0 Hz, 109.91, 85.06, 75.31, 1H), 3.00 (dd,J = 13.6, 3.6 72.31, 72.16, 70.41, Hz, 1H), 2.38 (s, 3H), 2.32 (s,56.29, 51.55, 47.18, 4H), 2.28-2.14 (m, 2H), 1.99- 34.80, 30.77 (q, J =1.90 (m, 1H), 1.90-1.79 29.1 Hz), 23.00 (q, J = (m, 2H), 1.47 (d, J =3.3 Hz), 21.01, 20.72, 6.4 Hz, 3H) 18.81 F63 — — HRMS-ESI ¹H NMR (CDCl₃)δ 8.58 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.4 Hz, 1H), 8.33 (d, J = 5.4171.70, 168.85, [M]⁺ Hz, 1H), 7.35-7.28 (m, 2H), 162.68, 159.43, calcdfor 7.09-6.91 (m, 8H), 5.21- 159.19, 141.10, C₃₁H₃₄N₂O₈, 5.11 (m, 1H),5.05 (dt, J = 8.6, 137.54, 136.27, 562.2315; 7.5 Hz, 1H), 4.30 (t, J =8.8 135.63, 129.71, found, Hz, 1H), 4.04 (dd, J = 11.7, 129.10, 128.98,562.2339 7.4 Hz, 1H), 3.90 (s, 3H), 3.61- 121.26, 115.49, 3.52 (m, 2H),3.42 (dd, J = 109.94, 81.91, 75.51, 11.7, 7.4 Hz, 1H), 2.99 (dd, J =72.32, 71.93, 56.31, 13.3, 2.9 Hz, 1H), 2.39 (s, 53.43, 51.57, 47.60,3H), 2.29 (s, 3H), 2.28-2.21 34.85, 21.01, 20.73, (m, 1H), 2.20-2.14 (m,1H), 19.03 1.39 (d, J = 6.4 Hz, 3H) F64 — — HRMS-ESI ¹H NMR (CDCl₃) δ8.54 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.4 Hz, 1 H), 8.32 (d, J = 5.4171.77, 168.86, [M]⁺ Hz, 1H), 7.13-7.04 (m, 4H), 162.63, 159.40, calcdfor 6.99 (d, J = 5.5 Hz, 1H), 5.04- 146.73, 141.20, C₃₀H₃₈N₂O₈, 4.88 (m,2H), 4.08 (td, J = 137.49, 137.15, 554.2628; 5.6, 3.6 Hz, 1H), 4.01 (dd,J = 135.49, 129.13, found, 11.6, 7.0 Hz, 1H), 3.89 (s, 128.99, 109.87,554.2639 3H), 3.50-3.41 (m, 2H), 3.35- 83.51, 83.43, 76.13, 3.24 (m,2H), 3.14 (dd, J = 73.22, 72.55, 56.29, 13.7, 3.5 Hz, 1H), 2.38 (s,51.85, 47.49, 34.67, 3H), 2.3 1 (s, 3H), 2.27 (dd, J = 32.73, 32.63,23.02, 13.5, 12.1 Hz, 1H), 1.91- 22.99, 21.02, 20.73, 1.63 (m, 7H),1.63-1.52 (m, 18.93 2H), 1.50 (d, J = 6.5 Hz, 3H) F65 — — HRMS-ESI ¹HNMR (CDCl₃) δ 8.57 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.5 Hz, 1H), 8.32 (d,J = 5.5 171.57, 168.83, [M]⁺ Hz, 1H), 7.55 (d, J = 8.0 Hz, 162.68,159.42, calcd for 2H), 7.31 (d, J = 8.0 Hz, 2H), 146.74, 144.26,C₂₉H₃₅F₃N₂O₈, 7.00 (d, J = 5.5 Hz, 1H), 5.05- 141.11, 137.52, 596.2346;4.94 (m, 2H), 4.00 (dd, J = 129.45, 128.49 (q, J = found, 11.7, 7.3 Hz,1H), 3.90 (s, 32.2 Hz), 125.37 (q, J = 596.2358 3H), 3.52-3.28 (m, 5H),3.21- 3.7 Hz), 109.91, 3.10 (m, 2H), 2.47-2.35 84.54, 79.41, 75.59, (m,4H), 2.02-1.83 (m, 2H), 72.48, 71.94, 56.29, 1.49 (d, J = 6.3 Hz, 3H),0.96 51.57, 47.42, 35.02, (d, J = 6.7 Hz, 6H) 29.18, 20.71, 19.46, 18.81F66 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.55 (d, J = ¹³C NMR (CDCl₃) δ (m/z)8.2 Hz, 1H), 8.32 (d, J = 5.4 171.66, 168.84, [M]⁺ Hz, 1H), 7.55 (d, J =8.0 Hz, 162.66, 159.41, calcd for 2H), 7.32 (d, J = 8.0 Hz, 2H), 146.75,144.59, C₃₀H₃₅F₃N₂O₈, 7.00 (d, J = 5.5 Hz, 1H), 5.05- 141.14, 137.51,608.2346; 4.88 (m, 2H), 4.18-3.97 129.41, 128.43 (q, J = found, (m, 2H),3.90 (s, 3H), 3.49- 32.4 Hz), 125.34 (q, J = 608.2360 3.37 (m, 2H),3.36-3.26 (m, 3.9 Hz), 124.30 (q, J = 2H), 3.21 (dd, J = 13.6, 3.5 271.9Hz), 109.91, Hz, 1H), 2.49-2.40 (m, 1H), 83.58, 83.29, 76.01, 2.38 (s,3H), 1.96-1.55 (m, 72.84, 72.75, 56.29, 9H), 1.51 (d, J = 6.5 Hz, 3H)51.83, 47.46, 35.08, 32.72, 32.63, 23.00, 20.72, 18.91 F67 — — HRMS-ESI¹H NMR (CDCl₃) δ 8.66- ¹⁹F NMR (CDCl₃) (m/z) 8.51 (m, 1H), 8.32 (d, J =5.4 δ −62.43 [M]⁺ Hz, 1H), 7.59-7.50 (m, 2H), calcd for 7.26 (d, J = 8.0Hz, 2H), 7.00 C₂₉H₃₃F₃N₂O₉, (d, J = 5.5 Hz, 1H), 5.14- 610.2138; 5.03(m, 2H), 4.98 (t, J = 9.3 found, Hz, 1H), 4.02 (dd, J = 11.7, 610.21397.3 Hz, 1H), 3.90 (s, 3H), 3.58- 3.42 (m, 3H), 2.75 (dd, J = 14.1, 3.9Hz, 1H), 2.61-2.52 (m, 1H), 2.44-2.32 (m, 4H), 2.17-2.06 (m, 1H), 1.34(d, J = 6.3 Hz, 3H), 1.21 (app dd, J = 7.0, 2.8 Hz, 6H) F68 — — HRMS-ESI¹H NMR (CDCl₃) δ 8.74- ¹³C NMR (CDCl₃) δ (m/z) 8.59 (m, 1H), 8.33 (d, J= 5.4 171.42, 168.84, [M]⁺ Hz, 1H), 7.00 (d, J = 5.4 Hz, 162.69, 159.40,calcd for 1H), 5.02 (dt, J = 8.4, 6.7 Hz, 146.76, 141.19, C₂₆H₄₀N₂O₈,1H), 4.95 (dq, J = 9.3, 6.4 Hz, 137.50, 109.88, 84.40, 508.2785; 1H),4.02 (dd, J = 11.8, 7.1 78.81, 75.80, 75.04, found, Hz, 1H), 3.90 (s,3H), 3.65 73.02, 56.29, 51.97, 508.2786 (dd, J = 10.6, 1.5 Hz, 1H),45.74, 35.99, 29.13, 3.59 (dd, J = 11.8, 6.4 Hz, 28.40, 26.73, 22.76,1H), 3.50 (dd, J = 10.7, 6.6 22.43, 20.73, 19.49, Hz, 1H), 3.34 (dd, J =8.4, 6.4 18.90 Hz, 1H), 3.26 (dd, J = 8.3, 6.3 Hz, 1H), 3.01 (t, J = 9.1Hz, 1H), 2.39 (s, 3H), 1.83 (hept, J = 6.6 Hz, 1H), 1.71-1.48 (m, 3H),1.44 (d, J = 6.4 Hz, 3H), 1.36-1.23 (m, 1H), 1.20- 1.07 (m, 2H), 0.92(d, J = 6.7 Hz, 6H), 0.88 (app dd, J = 6.6, 3.4 Hz, 6H) F69 — — HRMS-ESI¹H NMR (CDCl₃) δ 8.68 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.3 Hz, 1H), 8.34(d, J = 5.4 171.43, 168.85, [M]⁺ Hz, 1H), 7.12-7.04 (m, 2H), 162.72,159.43, calcd for 7.01 (d, J = 5.5 Hz, 1H), 6.85- 157.12, 146.78,C₂₉H₃₈N₂O₈, 6.75 (m, 2H), 5.18-5.01 141.15, 137.54, 542.2628; (m, 2H),4.17-4.02 (m, 2H), 130.30, 130.04, found, 3.91 (s, 3H), 3.72 (dd, J =115.23, 109.92, 82.03, 542.2634 10.9, 1.6 Hz, 1H), 3.62 (dd, J = 75.65,74.56, 73.01, 11.4, 6.7 Hz, 2H), 2.39 (s, 56.30, 51.93, 45.98, 3H), 2.28(s, 3H), 1.90-1.77 35.88, 28.04, 27.01, (m, 1H), 1.60-1.47 (m, 1H),22.78, 22.12, 20.73, 1.43-1.31 (m, 4H), 1.22- 20.43, 19.10 1.07 (m, 3H),0.78 (d, J = 6.6 Hz, 3H), 0.74 (d, J = 6.6 Hz, 3H) F70 — — HRMS-ESI ¹HNMR (CDCl₃) δ 8.66 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.4 Hz, 1H), 8.33 (d,J = 5.4 171.42, 168.84, [M]⁺ Hz, 1H), 7.00 (d, J = 5.5 Hz, 162.69,159.40, calcd for 1H), 5.02 (ddd, J = 8.4, 7.2, 146.75, 141.18,C₂₅H₃₈N₂O₈, 6.4 Hz, 1H), 4.94 (dq, J = 9.2, 137.50, 109.88, 84.69,494.2628; 6.4 Hz, 1H), 4.02 (dd, J = 75.81, 75.01, 73.95, found, 11.8,7.1 Hz, 1H), 3.90 (s, 73.02, 56.29, 51.95, 494.2632 3H), 3.70-3.41 (m,5H), 3.02 45.72, 35.96, 28.37, (t, J = 9.2 Hz, 1H), 2.39 (s, 26.81,23.44, 22.77, 3H), 1.71-1.48 (m, 5H), 1.45 22.37, 20.72, 18.87, (d, J =6.3 Hz, 3H), 1.36- 10.69 1.21 (m, 1H), 1.22-1.08 (m, 2H), 0.94 (t, J =7.4 Hz, 3H), 0.88 (app dd, J = 6.6, 3.9 Hz, 6H) F71 — — HRMS-ESI ¹H NMR(CDCl₃) δ 8.65 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.2 Hz, 1H), 8.34 (d, J =5.4 171.44, 168.85, [M]⁺ Hz, 1H), 7.00 (d, J = 5.5 Hz, 162.67, 159.39,calcd for 1H), 5.03-4.89 (m, 2H), 4.06 146.74, 141.25, C₂₇H₄₀N₂O₈, (dd,J = 11.8, 6.6 Hz, 1H), 137.49, 109.85, 83.57, 520.2785; 4.02-3.95 (m,1H), 3.90 (s, 83.18, 76.33, 76.13, found, 3H), 3.68-3.47 (m, 3H), 3.1673.53, 56.28, 52.31, 520.2802 (t, J = 8.5 Hz, 1H), 2.39 (s, 46.18,36.66, 32.62, 3H), 1.79-1.59 (m, 7H), 1.59- 32.55, 28.46, 26.85, 1.48(m, 4H), 1.45 (d, J = 23.06, 23.02, 22.73, 6.5 Hz, 3H), 1.37-1.22 (m,1H), 22.50, 20.73, 18.97 1.18-1.01 (m, 2H), 0.88 (app dd, J = 6.6, 4.3Hz, 6H) F72 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.58 (d, J = ¹⁹F NMR (CDCl₃)(m/z) 8.6 Hz, 1H), 8.32 (d, J = 5.4 δ −134.78 [M]⁺ Hz, 1H), 7.00 (d, J =5.5 Hz, (d, J = 20.5 calcd for 1H), 6.81 (dd, J = 8.3, 6.4 Hz, Hz),−163.99 (t, J = C₂₈H₃₃F₃N₂O₈, 2H), 5.06-4.91 (m, 2H), 4.02 21.0 Hz)582.2189; (dd, J = 11.7, 7.2 Hz, 1H), found, 3.90 (s, 3H), 3.51-3.36 (m,4H), 582.2197 3.29 (dd, J = 8.3, 6.3 Hz, 1H), 3.10 (t, J = 9.0 Hz, 1H),3.04 (dd, J = 13.8, 3.4 Hz, 1H), 2.38 (s, 3H), 2.31 (dd, J = 13.8, 11.8Hz, 1H), 1.87 (dt, J = 13.3, 6.7 Hz, 2H), 1.48 (d, J = 6.4 Hz, 3H), 0.95(app dd, J = 6.7, 1.3 Hz, 6H) F73 93-97 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.57(d, J = ¹³C NMR (CDCl₃) δ (m/z) 7.7 Hz, 1H), 8.32 (d, J = 5.4 176.30,171.57, [M]⁺ Hz, 1H), 7.35 (d, J = 1.9 Hz, 168.84, 162.67, calcd for1H), 7.25-7.07 (m, 2H), 7.00 159.44, 146.74, C₂₈H₃₂Cl₂N₂O₉, (d, J = 5.5Hz, 1H), 5.21- 141.02, 137.54, 610.1485; 4.78 (m, 3H), 4.06 (dd, J =135.21, 134.88, found, 11.7, 7.3 Hz, 1H), 3.90 (s, 132.93, 132.38,610.1498 3H), 3.63-3.28 (m, 3H), 2.79 129.47, 127.11, (dd, J = 13.9, 3.5Hz, 1H), 109.96, 76.57, 73.96, 2.61 (dt, J = 14.0, 7.0 Hz, 72.41, 71.29,56.30, 1H), 2.55-2.44 (m, 1H), 2.39 (s, 51.52, 44.02, 34.22, 3H),2.18-2.10 (m, 1H), 1.34 32.33, 20.72, 18.97, (d, J = 6.3 Hz, 3H), 1.22(d, J = 18.16 7.0 Hz, 6H) F74 69-73 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.58 (d,J = ¹³C NMR (CDCl₃) δ (m/z) 1.1 Hz, 1H), 8.32 (d, J = 5.4 171.54,168.83, [M]⁺ Hz, 1H), 7.36 (d, J = 1.7 Hz, 162.68, 159.41, calcd for1H), 7.24-7.11 (m, 2H), 7.00 146.75, 141.11, C₂₈H₃₄Cl₂N₂O₈, (d, J = 5.5Hz, 1H), 5.00 (p, J = 137.51, 136.18, 596.1692; 7.5, 7.0 Hz, 2H), 4.02(dd, J = 135.04, 132.53, found, 11.7, 7.3 Hz, 1H), 3.89 (s, 132.14,129.33, 596.1707 3H), 3.58-3.23 (m, 5H), 3.23- 127.08, 109.92, 84.94,3.02 (m, 2H), 2.60-2.46 79.71, 75.64, 72.53, (m, 1H), 2.38 (s, 3H),2.08- 71.92, 56.30, 51.64, 1.98 (m, 1H), 1.89 (dq, J = 45.90, 32.12,29.17, 13.2, 6.6 Hz, 1H), 1.49 (d, J = 20.72, 19.49, 18.77 6.4 Hz, 3H),0.95 (dd, J = 6.7, 1.1 Hz, 6H) F75 55-59 — HRMS-ESI ¹H NMR (CDCl₃) δ8.57 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 1.1 Hz, 1H), 8.32 (d, J = 5.4171.57, 168.84, [M]⁺ Hz, 1H), 7.36 (d, J = 1.8 Hz, 162.68, 159.42, calcdfor 1H), 7.25-7.10 (m, 2H), 7.00 146.75, 141.12, C₂₉H₃₆Cl₂N₂O₈, (d, J =5.5 Hz, 1H), 5.07- 137.51, 136.17, 610.1849; 4.89 (m, 2H), 4.02 (dd, J =135.04, 132.55, found, 11.7, 7.3 Hz, 1H), 3.90 (s, 132.12, 129.34,610.1862 3H), 3.75-3.62 (m, 1H), 3.61- 127.08, 109.92, 85.22, 3.50 (m,1H), 3.42-3.37 73.24, 72.50, 71.87, (m, 3H), 3.23-2.97 (m, 2H), 56.30,51.61, 45.87, 2.54 (dd, J = 13.6, 12.2 Hz, 32.18, 31.59, 29.97, 1H),2.39 (s, 3H), 2.06-1.96 28.33, 22.66, 20.72, (m, 1H), 1.62-1.57 (m, 2H),18.72, 14.01 1.49 (d, J = 6.4 Hz, 3H), 1.43- 1.19 (m, 4H), 0.89 (d, J =6.7 Hz, 3H) F76  97-101 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.59 (d, J = ¹³C NMR(CDCl₃) δ (m/z) 7.8 Hz, 1H), 8.32 (d, J = 5.4 171.62, 168.84, [M]⁺ Hz,1H), 7.32 (s, 1H), 7.14 (d, 162.71, 159.45, calcd for J = 1.1 Hz, 2H),7.10 (d, J = 156.98, 146.77, C₃₁H₃₂Cl₂N₂O₈, 8.3 Hz, 2H), 7.00 (d, J =5.5 141.08, 137.55, 630.1536; Hz, 1H), 6.88 (d, J = 8.6 Hz, 135.80,134.97, found, 2H), 5.22-5.10 (m, 1H), 5.04 132.67, 132.22, 630.1531 (q,J = 7.6 Hz, 1H), 4.28 (t, J = 130.64, 130.18, 8.8 Hz, 1H), 4.08 (dd, J =129.37, 127.03, 11.7, 7.4 Hz, 1H), 3.89 (s, 115.16, 109.97, 81.99, 3H),3.56 (dd, J = 11.1, 6.3 75.40, 72.37, 71.35, Hz, 1H), 3.48 (d, J = 10.3Hz, 56.31, 51.54, 46.13, 1H), 3.40 (dd, J = 11.6, 32.39, 20.73, 20.44,7.6 Hz, 1H), 3.04 (dd, J = 18.94 13.7, 3.5 Hz, 1H), 2.57-2.45 (m, 1H),2.39 (s, 3H), 2.29 (s, 3H), 2.28-2.17 (m, 1H), 1.40 (d, J = 6.4 Hz, 3H)F77 66-69 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.64 (d, J = ¹³C NMR (CDCl₃) δ(m/z) 7.8 Hz, 1H), 8.33 (d, J = 5.4 176.17, 171.52, [M]⁺ Hz, 1H), 7.01(d, J = 5.5 Hz, 168.81, 162.67, calcd for 1H), 5.12-5.04 (m, 1H), 5.01159.43, 146.74, C₂₇H₃₈N₂O₉, (dd, J = 9.3, 6.4 Hz, 1H), 141.07, 137.53,534.2577; 4.79 (t, J = 9.3 Hz, 1H), 109.95, 74.32, 73.78, found, 4.07(dd, J = 11.7, 7.3 Hz, 72.68, 56.29, 51.76, 534.2581 1H), 3.90 (s, 3H),3.72 (d, 43.57, 37.19, 35.02, J = 10.7 Hz, 1H), 3.65-3.54 34.25, 33.62,32.13, (m, 2H), 2.58 (p, J = 7.0 Hz, 25.01, 20.70, 18.96, 1H), 2.39 (s,3H), 1.90-1.69 18.31 (m, 4H), 1.61-1.45 (m, 4H), 1.30 (d, J = 6.4 Hz,3H), 1.20 (d, J = 7.0 Hz, 6H), 1.11-0.94 (m, 4H) F78 56-59 — HRMS-ESI ¹HNMR (CDCl₃) δ 8.62 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 7.5 Hz, 1H), 8.34 (d,J = 5.4 171.59, 168.85, [M]⁺ Hz, 1H), 7.00 (d, J = 5.5 Hz, 162.68,159.41, calcd for 1H), 5.04-4.97 (m, 1H), 4.94 146.75, 141.20,C₂₇H₄₀N₂O₈, (dd, J = 9.1, 6.4 Hz, 1H), 109.88, 84.88, 79.01, 520.2785;4.05 (dd, J = 11.7, 7.2 Hz, 75.87, 74.17, 72.68, found, 1H), 3.90 (s,3H), 3.62 (d, J = 56.29, 51.80, 44.70, 520.2798 9.6 Hz, 1H), 3.56-3.47(m, 2H), 37.39, 34.95, 33.89, 3.36 (dd, J = 8.3, 6.2 Hz, 1H), 32.03,29.14, 25.09, 3.23 (dd, J = 8.3, 6.6 Hz, 1H), 20.72, 19.53, 18.86 2.96(t, J = 9.0 Hz, 1H), 2.39 (s, 3H), 1.93-1.71 (m, 4H), 1.69-1.47 (m, 5H),1.44 (d, J = 6.4 Hz, 3H), 1.30-1.19 (m, 2H), 1.15-1.01 (m, 2H), 0.92(dd, J = 6.7, 4.5 Hz, 6H) F79 46-51 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.63 (d,J = ¹³C NMR (CDCl₃) δ (m/z) 7.6 Hz, 1H), 8.33 (d, J = 5.4 171.58,168.81, [M]⁺ Hz, 1H), 7.00 (d, J = 5.5 Hz, 162.67, 159.40, calcd for1H), 5.01 (q, J = 7.1 Hz, 1H), 146.75, 141.17, C₂₈H₄₂N₂O₈, 4.93 (dd, J =9.1, 6.4 Hz, 137.49, 109.90, 85.23, 534.2941; 1H), 4.04 (dd, J = 11.7,7.2 Hz, 75.84, 74.21, 72.50, found, 1H), 3.90 (s, 3H), 3.67-3.41 56.28,51.79, 44.69, 534.2945 (m, 5H), 2.96 (t, J = 9.1 Hz, 1H), 37.39, 35.09,33.85, 2.39 (s, 3H), 1.95-1.83 (m, 1H), 32.05, 29.94, 28.36, 1.82-1.71(m, 2H), 1.67-1.47 (m, 25.06, 22.56, 20.70, 8H), 1.44 (d, J = 6.4 Hz,3H), 18.81, 14.00 1.37-1.23 (m, 5H), 1.15-1.01 (m, 2H), 0.90 (t, J = 7.2Hz, 3H) F80 — — HRMS-FAB ¹H NMR (CDCl₃) δ 8.56 (d, J = ¹³C NMR (CDCl₃) δ(m/z) 7.8 Hz, 1H), 8.31 (d, J = 5.4 171.68, 168.84, [M + Na]⁺ Hz, 1H),7.08 (d, J = 2.4 Hz, 162.66, 159.41, calcd for 4H), 6.98 (d, J = 5.5 Hz,1H), 146.75, 141.13, C₂₉H₃₈N₂O₈Na, 4.99 (m, 2H), 3.98 (dd, J = 137.49,136.82, 565.2520; 11.7, 7.4 Hz, 1H), 3.88 (s, 3H), 135.54, 129.13,found, 3.40 (m, 6H), 3.11 (m, 2H), 129.06, 109.91, 84.57, 565.2516 2.38(s, 3H), 2.31 (s, 3H), 79.12, 75.72, 72.32, 2.26 (m, 1H), 1.90 (ddd, J =72.25, 56.30, 51.59, 19.8, 13.5, 6.8 Hz, 2H), 1.48 47.41, 34.62, 29.19,(d, J = 6.4 Hz, 3H), 0.95 21.03, 20.73, 19.51, (d, J = 6.7 Hz, 6H) 18.85F81 45-50 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.49 (d, J = — (m/z) 8.0 Hz, 1H),8.29 (d, J = 5.4 [M + H]⁺ Hz, 1H), 7.33-7.24 (m, 2H), calcd for7.22-7.15 (m, 3H), 6.96 (d, J = C₃₁H₄₁N₂O₉, 5.4 Hz, 1H), 5.78-5.69 (m,2H), 585.2807; 5.05-4.93 (m, 2H), 4.19-4.08 found, (m, 1H), 4.02-3.92(m, 1H), 585.2831 3.91 (s, 3H), 3.76-3.55 (m, 3H), 3.22 (app t, J = 8.3Hz, 1H), 2.76 (ddd, J = 13.8, 11.1, 4.7 Hz, 1H), 2.60 (ddd, J = 13.7,10.5, 6.1 Hz, 1H), 2.11-1.96 (m, 4H), 1.78-1.39 (m, 13H) F82 — —HRMS-ESI ¹H NMR (CDCl₃) δ 8.49 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.0 Hz,1H), 8.29 (d, J = 5.4 171.51, 170.27, [M + H]⁺ Hz, 1H), 7.33-7.23 (m,2H), 163.21, 160.20, calcd for 7.23-7.14 (m, 3H), 6.96 (d, J = 145.81,143.92, C₃₀H₄₁N₂O₉, 5.4 Hz, 1H), 5.74 (ab q, J = 7.9 142.17, 142.15,573.2807; Hz, 2H), 5.05 (app dt, J = 8.1, 128.37, 125.81, found, 6.8 Hz,1H), 4.97 (dq, J = 109.71, 89.40, 84.33, 573.2807 9.0, 6.4 Hz, 1H), 4.11(dd, J = 78.62, 75.65, 74.59, 11.7, 7.1 Hz, 1H), 3.91 (s, 73.05, 56.20,52.17, 3H), 3.74 (dd, J = 10.9, 1.7 45.13, 33.29, 30.99, Hz, 1H),3.67-3.57 (m, 2H), 29.07, 20.88, 19.44, 3.29 (dd, J = 8.4, 6.4 Hz,19.41, 18.88 1H), 3.23 (dd, J = 8.3, 6.4 Hz, 1H), 3.07 (app t, J = 9.1Hz, 1H), 2.77 (ddd, J = 13.5, 10.9, 4.7 Hz, 1H), 2.56 (ddd, J = 13.7,10.3, 6.5 Hz, 1H), 2.07 (s, 3H), 1.97 (dddd, J = 13.7, 10.8, 6.6, 3.0Hz, 1H), 1.85-1.77 (m, 1H), 1.77-1.66 (m, 1H), 1.51 (ddd, J = 10.3, 8.4,5.1 Hz, 1H), 1.45 (d, J = 6.4 Hz, 3H), 0.90 (appd, J = 6.7 Hz, 6H) F8358-64 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.37 (d, J = — (m/z) 8.1 Hz, 1H), 8.24(d, J = 5.3 [M + H]⁺ Hz, 1H), 8.02-7.94 (m, 1H), calcd for 7.89-7.81 (m,1H), 7.74 (d, J = C₃₃H₃₉N₂O₁₀, 8.2 Hz, 1H), 7.56-7.43 (m, 2H), 623.2599;7.40 (dd, J = 8.2, 7.0 Hz, 1H), found, 7.30 (dd, J = 7.1, 1.2 Hz, 1H),623.2611 6.92 (d, J = 5.4 Hz, 1H), 5.71 (d, J = 6.5 Hz, 2H), 5.17-5.06(m, 3H), 4.04 (dd, J = 11.6, 7.4 Hz, 1H), 3.89 (s, 3H), 3.60 (d, J = 4.2Hz, 2H), 3.40 (dd, J = 11.7, 7.1 Hz, 1H), 3.23 (dd, J = 14.2, 3.1 Hz,1H), 2.77-2.63 (m, 2H), 2.29 (app ddt, J = 12.2, 8.1, 3.9 Hz, 1H), 2.04(s, 3H), 1.39 (d, J = 5.6 Hz, 3H), 1.29 (app dd, J = 7.0, 3.9 Hz, 6H)F84 61-68 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.33 (d, J = ¹⁹F NMR (CDCl₃) (m/z)8.2 Hz, 1H), 8.23 (d, J = 5.4 δ −66.36 [M + H]⁺ Hz, 1H), 8.16-8.08 (m,1H), calcd for 7.85 (dd, J = 7.9, 1.6 Hz, C₃₃H₃₈F₃N₂O₉, 1H), 7.74 (d, J= 8.1 Hz, 1H), 7.55- 663.2524; 7.43 (m, 2H), 7.40 (dd, J = 8.2, found,7.0 Hz, 1H), 7.33 (dd, J = 7.0, 663.2538 1.3 Hz, 1H), 6.92 (d, J = 5.4Hz, 1H), 5.74-5.68 (m, 2H), 5.09-4.90 (m, 2H), 4.07 (dd, J = 11.7, 7.5Hz, 1H), 3.88 (s, 4H), 3.77 (app dt, J = 8.8, 6.0 Hz, 1H), 3.58 (dd, J =13.6, 2.9 Hz, 1H), 3.52 (dd, J = 10.8, 5.7 Hz, 1H), 3.46- 3.38 (m, 1H),3.36-3.24 (m, 2H), 2.82-2.71 (m, 1H), 2.40- 2.23 (m, 2H), 2.15-1.90 (m,6H), 1.54 (d, J = 6.4 Hz, 3H) F85 83-88 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.36(d, J = — (m/z) 8.2 Hz, 1H), 8.23 (d, J = 5.3 [M + H]⁺ Hz, 1H),8.12-8.05 (m, 1H), calcd for 7.85-7.78 (m, 1H), 7.70 (d, J = C₃₆H₃₉N₂O₉,8.1 Hz, 1H), 7.55-7.41 (m, 2H), 643.2650; 7.36 (dd, J = 8.2, 7.0 Hz,1H), found, 7.28 (dd, J = 7.0, 1.3 Hz, 1H), 643.2639 7.18-7.10 (m, 2H),7.06-6.99 (m, 2H), 6.91 (d, J = 5.4 Hz, 1H), 5.72 (s, 2H), 5.20-5.03 (m,2H), 4.44 (app t, J = 9.1 Hz, 1H), 4.15-4.06 (m, 1H), 3.87 (s, 3H),3.66-3.48 (m, 3H), 3.34 (dd, J = 11.6, 7.8 Hz, 1H), 2.69 (app t, J =12.9 Hz, 1H), 2.38- 2.25 (m, 4H), 2.05 (s, 3H), 1.44 (d, J = 6.4 Hz, 3H)F86 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.31 (d, J = ¹³C NMR (CDCl₃) δ (m/z)8.2 Hz, 1H), 8.22 (d, J = 5.4 171.96, 170.27, [M + H]⁺ Hz, 1H), 8.12(dd, J = 8.3, 1.4 163.16, 160.17, calcd for Hz, 1H), 7.83 (dd, J = 7.9,1.5 145.76, 143.88, C₃₄H₄₁N₂O₉, Hz, 1H), 7.72 (d, J = 8.0 Hz, 142.15,136.10, 621.2807; 1H), 7.56-7.43 (m, 2H), 7.39 133.99, 132.12, found,(dd, J = 8.1, 7.0 Hz, 1H), 7.34 128.76, 127.71, 621.2824 (dd, J = 7.0,1.4 Hz, 1H), 6.91 127.02, 125.95, (d, J = 5.4 Hz, 1H), 5.75- 125.49,125.33, 5.67 (m, 2H), 5.04-4.90 (m, 2H), 124.10, 109.69, 89.39,4.29-4.19 (m, 1H), 4.08 (dd, J = 84.12, 83.39, 76.62, 11.6, 7.2 Hz, 1H),3.87 (s, 3H), 72.18, 56.19, 51.76, 3.74 (dd, J = 13.5, 2.8 Hz, 1H),46.75, 33.00, 32.52, 3.56-3.36 (m, 3H), 3.23 (dd, J = 32.42, 23.06,23.00, 11.6, 7.9 Hz, 1H), 2.80-2.68 20.86, 18.99 (m, 1H), 2.10-1.95 (m,4H), 1.93-1.79 (m, 6H), 1.65-1.53 (m, 5H) F87 — — HRMS-ESI ¹H NMR(CDCl₃) δ 8.34 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.2 Hz, 1H), 8.23 (d, J =5.3 171.88, 170.25, [M + H]⁺ Hz, 1H), 8.20 (dd, J = 8.5, 1.4 163.15,160.15, calcd for Hz, 1H), 7.83 (dd, J = 7.9, 1.7 145.75, 143.87,C₃₃H₄₁N₂O₉, Hz, 1H), 7.72 (d, J = 8.1 Hz, 142.08, 135.79, 609.2807; 1H),7.54-7.42 (m, 2H), 7.39 133.96, 132.12, found, (dd, J = 8.1, 7.0 Hz,1H), 7.33 128.70, 127.78, 609.2813 (dd, J = 7.0, 1.3 Hz, 1H), 6.91127.05, 125.87, (d, J = 5.4 Hz, 1H), 5.71 (s, 125.48, 125.28, 2H),5.09-5.00 (m, 1H), 5.00- 124.23, 109.68, 89.36, 4.91 (m, 1H), 4.05 (dd,J = 85.24, 80.79, 76.12, 11.6, 7.5 Hz, 1H), 3.88 (s, 3H), 71.98, 71.49,56.17, 3.73-3.64 (m, 1H), 3.60 51.59, 46.91, 32.60, (dd, J = 8.4, 6.5Hz, 1H), 29.35, 20.85, 19.60, 3.56-3.40 (m, 3H), 3.35-3.22 19.58, 18.79(m, 2H), 2.71 (dd, J = 13.7, 11.9 Hz, 1H), 2.16-1.97 (m, 5H), 1.55 (d, J= 6.3 Hz, 3H), 1.03 (app dd, J = 6.7, 2.2 Hz, 6H) F88 39-43 — HRMS-ESI¹H NMR (CDCl₃) δ 8.40 (d, J = — (m/z) 8.2 Hz, 1H), 8.26 (d, J = 5.4 [M +H]⁺ Hz, 1H), 7.14-7.04 (m, 4H), calcd for 6.94 (d, J = 5.4 Hz, 1H),5.76- C₃₁H₄₃N₂O₉, 5.67 (m, 2H), 5.08-4.92 587.2963; (m, 2H), 4.00 (dd, J= 11.7, found, 7.3 Hz, 1H), 3.89 (s, 3H), 587.2981 3.67 (app dt, J =8.7, 6.6 Hz, 1H), 3.59-3.48 (m, 2H), 3.48- 3.36 (m, 2H), 3.19-3.06 (m,2H), 2.35-2.22 (m, 4H), 2.05 (s, 3H), 1.99-1.86 (m, 1H), 1.67-1.54 (m,2H), 1.50 (d, J = 6.3 Hz, 3H), 1.43-1.27 (m, 4H), 0.94-0.85 (m, 3H) F8943-47 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.42 (d, J = — (m/z) 8.1 Hz, 1H), 8.26(d, J = 5.4 [M + H]⁺ Hz, 1H), 7.09 (d, J = 7.7 Hz, calcd for 2H), 7.03(d, J = 8.0 Hz, 2H), C₃₀H₃₉N₂O₁₀, 6.95 (d, J = 5.4 Hz, 1H), 5.71587.2599; (s, 2H), 5.14-5.02 (m, 2H), found, 4.96 (app t, J = 9.3 Hz,1H), 587.2625 4.02 (dd, J = 11.7, 7.3 Hz, 1H), 3.90 (s, 3H), 3.65-3.57(m, 1H), 3.57-3.44 (m, 2H), 2.68 (dd, J = 14.0, 3.6 Hz, 1H), 2.60 (appp, J = 7.0 Hz, 1H), 2.31 (s, 3H), 2.23 (dd, J = 13.9, 11.4 Hz, 1H),2.14- 2.02 (m, 4H), 1.34 (d, J = 6.3 Hz, 3H), 1.22 (app dd, J = 7.0, 1.6Hz, 6H) F90 59-64 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.43 (d, J = — (m/z) 8.1Hz, 1H), 8.27 (d, J = 5.4 [M + H]⁺ Hz, 1H), 7.16-7.07 (m, 2H), calcd for7.03-6.92 (m, 3H), 5.76-5.68 C₂₉H₃₄FN₂O₁₀, (m, 2H), 5.08 (m, 2H), 4.96589.2192; (app t, J = 9.3 Hz, 1H), 4.03 found, (dd, J = 11.7, 7.2 Hz,1H), 589.2220 3.91 (s, 3H), 3.65-3.57 (m, 1H), 3.57-3.47 (m, 2H), 2.73(dd, J = 14.1, 3.9 Hz, 1H), 2.29 (dd, J = 14.1, 11.1 Hz, 1H), 2.14-2.00(m, 4H), 1.70-1.58 (m, 1H), 1.35 (d, J = 6.3 Hz, 3H), 1.06-1.00 (m, 2H),0.95- 0.89 (m, 2H) F91 52-56 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.42 (d, J = —(m/z) 8.1 Hz, 1H), 8.27 (d, J = [M + H]⁺ 5.4 Hz, 1H), 7.15-7.06 (m,calcd for 2H), 7.02-6.93 (m, 3H), 5.72 C₂₉H₃₆FN₂O₁₀, (s, 2H), 5.09 (m,2H), 4.97 591.2349; (app t, J = 9.3 Hz, 1H), found, 4.04 (dd, J = 11.7,7.3 Hz, 591.2368 1H), 3.91 (s, 3H), 3.63-3.45 (m, 3H), 2.68 (dd, J =14.1, 3.7 Hz, 1H), 2.59 (app hept, J = 7.0 Hz, 1H), 2.28 (dd, J = 14.1,11.3 Hz, 1H), 2.11-1.99 (m, 4H), 1.34 (d, J = 6.3 Hz, 3H), 1.22 (app dd,J = 7.0, 1.8 Hz, 6H) F92 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.50 (d, J = ¹³CNMR (CDCl₃) δ (m/z) 8.0 Hz, 1H), 8.29 (d, J = 5.3 174.15, 171.44, [M]⁺Hz, 1H), 7.3 1-7.24 (m, 2H), 170.28, 163.22, calcd for 7.22-7.11 (m,3H), 6.96 (d, J = 160.23, 145.79, C₃₀H₃₆N₂O₁₀, 5.4 Hz, 1H), 5.77-5.70(m, 144.01, 142.11, 584.2377; 2H), 5.15-5.08 (m, 1H), 5.07- 141.76,128.39, found, 4.98 (m, 1H), 4.94 (t, J = 9.3 128.32, 125.92, 584.2370Hz, 1H), 4.11 (dd, J = 11.8, 109.74, 89.43, 76.28, 7.2 Hz, 1H), 3.92 (s,3H), 3.88- 74.55, 74.33, 73.21, 3.81 (m, 1H), 3.74-3.64 56.21, 52.21,43.89, (m, 2H), 2.79-2.66 (m, 1H), 32.46, 31.32, 20.88, 2.53-2.41 (m,1H), 2.08 (s, 18.31, 12.87, 8.54 3H), 1.88-1.79 (m, 1H), 1.65- 1.58 (m,2H), 1.57-1.45 (m, 1H), 1.33 (d, J = 6.2 Hz, 3H), 1.05- 0.96 (m, 2H),0.93-0.86 (m, 2H) F93 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.39 (d, J = ¹³C NMR(CDCl₃) δ (m/z) 8.2 Hz, 1H), 8.27 (d, J = 5.3 171.68, 170.26, [M]⁺ Hz,1H), 7.19-7.09 (m, 2H), 163.18, 161.45 (d, J = calcd for 7.04-6.90 (m,3H), 5.76-5.67 244.3 Hz), 160.21, C₂₉H₃₄F₄N₂O₉, (m, 2H), 5.07-4.93 (m,2H), 145.78, 143.94, 630.2200; 4.04 (dd, J = 11.7, 7.3 Hz, 1H), 142.07,135.18 (d, J = found, 3.91 (s, 3H), 3.77-3.67 (m, 1H), 3.0 Hz), 130.45(d, J = 630.2211 3.67-3.54 (m, 1H), 3.48-3.37 (m, 7.7 Hz), 127.07 (q, J= 3H), 3.17 (t, J = 8.9 Hz, 1H), 276.0 Hz), 115.29 (d, J = 3.01 (dd, J =13.8, 3.6 Hz, 1H), 21.1 Hz), 109.73, 89.38, 2.42-2.30 (m, 1H), 2.29-2.1585.07, 75.23, 72.44, (m, 2H), 2.06 (s, 3H), 1.98- 71.94, 70.62, 56.20,1.80 (m, 3H), 1.48 (d, J = 6.4 Hz, 51.81, 47.46, 34.44, 3H) 30.73 (q, J= 29.3 Hz), 23.00 (q, J = 3.1 Hz), 20.86, 18.79 F94 — — HRMS-ESI ¹H NMR(CDCl₃) δ 8.38 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.1 Hz, 1H), 8.27 (d, J =5.3 171.80, 170.26, [M]⁺ Hz, 1H), 7.19-7.09 (m, 2H), 7.02- 163.15,161.35 (d, J = calcd for 6.89 (m, 3H), 5.77-5.68 (m, 2H), 243.7 Hz),160.20, C₃₀H₃₇FN₂O₉ 5.05-4.91 (m, 2H), 4.13-4.02 (m, 145.76, 143.94,588.2483; 2H), 3.90 (s, 3H), 3.50-3.38 (m, 142.14, 135.90 (d, J = found,2H), 3.38-3.27 (m, 2H), 3.14 (dd, 3.1 Hz), 130.47 (d, J = 588.2504 J =13.6, 3.5 Hz, 1H), 2.33 (dd, J = 7.5 Hz), 115.20 (d, J = 13.7, 12.2 Hz,1H), 2.06 21.4 Hz), 109.69, 89.40, (s, 3H), 1.90-1.68 (m, 7H), 83.56,83.33, 76.08, 1.62-1.47 (m, 5H) 73.00, 72.70, 56.19, 52.08, 47.76,34.36, 32.71, 32.62, 23.00, 20.86, 18.91 F95 — — HRMS-ESI ¹H NMR (CDCl₃)δ 8.40 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.2 Hz, 1H), 8.3 1-8.22 (m,171.71, 170.26, [M]⁺ 1H), 7.19-7.08 (m, 2H), 7.03- 163.18, 161.40 (d, J= calcd for 6.92 (m, 3H), 5.76-5.68 244.0 Hz), 160.21, C₃₀H₃₉FN₂O₉, (m,2H), 5.07-4.90 (m, 2H), 145.78, 143.94, 590.2640; 4.02 (dd, J = 11.7,7.3 Hz, 142.13, 135.56 (d, J = found, 1H), 3.90 (s, 3H), 3.74-3.61 3.2Hz), 130.52 (d, J = 590.2658 (m, 1H), 3.57-3.49 (m, 1H), 7.7 Hz), 115.21(d, J = 3.49-3.35 (m, 3H), 3.20- 21.2 Hz), 109.71, 3.05 (m, 2H), 2.32(dd, J = 89.40, 84.91, 75.65, 13.7, 11.7 Hz, 1H), 2.06 (s, 72.89, 72.50,72.18, 3H), 1.95-1.82 (m, 1H), 1.66- 56.19, 51.85, 47.60, 1.53 (m, 2H),1.52-1.44 (m, 3H), 34.40, 30.00, 28.34, 1.41-1.30 (m, 4H), 0.96-0.8722.58, 20.86, 18.77, (m, 3H) 14.01 F96 — — HRMS-ESI ¹H NMR (CDCl₃) δ8.40 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.1 Hz, 1H), 8.26 (d, J = 5.3171.72, 170.25, [M]⁺ Hz, 1H), 7.15 (dd, J = 8.5, 163.17, 161.39 (d, J =calcd for 5.5 Hz, 2H), 7.02-6.89 (m, 3H), 243.9 Hz), 160.20,C₂₉H₃₇FN₂O₉, 5.74-5.70 (m, 2H), 5.01 145.78, 143.92, 576.2483; (ddd, J =15.6, 8.7, 6.8 Hz, 142.12, 135.59 (d, J = found 2H), 4.03 (dd, J = 11.7,7.3 3.0 Hz), 130.52 (d, J = 576.2491 Hz, 1H), 3.90 (s, 3H), 3.52- 8.0Hz), 115.20 (d, J = 3.36 (m, 4H), 3.33 (dd, J = 8.4, 21.2 Hz), 109.71,6.4 Hz, 1H), 3.18-3.06 (m, 2H), 89.39, 84.55, 79.34, 2.31 (dd, J = 13.7,11.7 Hz, 75.64, 72.45, 72.07, 1H), 2.06 (s, 3H), 1.98-1.82 56.19, 51.84,47.69, (m, 2H), 1.50 (d, J = 6.4 Hz, 34.30, 29.18, 20.86, 3H), 0.96 (d,J = 6.7 Hz, 6H) 19.48, 18.81 F97 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.43 (d,J = ¹³C NMR (CDCl₃) δ (m/z) 8.1 Hz, 1H), 8.27 (d, J = 5.3 174.27,171.65, [M]⁺ Hz, 1H), 7.12-7.08 (m, 2H), 170.27, 163.16, calcd for7.07-7.02 (m, 2H), 6.94 (d, J = 160.21, 145.75, C₃₀H₃₆N₂O₁₀, 5.4 Hz,1H), 5.74-5.67 (m, 2H), 143.99, 142.07, 584.2730; 5.08 (s, 2H), 4.95 (t,J = 9.3 135.90, 135.80, found, Hz, 1H), 4.01 (dd, J = 11.7, 7.3 129.20,128.90, 584.2734 Hz, 1H), 3.90 (s, 3H), 3.63 (dd, 109.71, 89.42, 76.98,J = 10.6, 1.6 Hz, 1H), 3.57-3.44 74.24, 72.72, 56.20, (m, 2H), 2.73 (dd,J = 14.0, 3.7 52.01, 45.85, 34.56, Hz, 1H), 2.31 (s, 3H), 2.29-2.1721.02, 20.87, 18.27, (m, 1H), 2.15-2.07 (m, 1H), 2.06 12.88, 8.64, 8.61(s, 2H), 1.70-1.60 (m, 2H), 1.35 (d, J = 6.3 Hz, 3H), 1.09- 1.00 (m,2H), 0.96-0.87 (m, 2H) F98 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.44 (d, J =¹³C NMR (CDCl₃) δ (m/z) 8.1 Hz, 1H), 8.27 (d, J = 5.4 174.26, 171.56,[M]⁺ Hz, 1H), 7.55 (d, J = 8.0 Hz, 2H), 170.26, 163.19, calcd for 7.28(d, J = 7.9 Hz, 2H), 160.23, 145.77, C₃₀H₃₃F₃N₂O₁₀, 6.95 (d, J = 5.4 Hz,1H), 5.72 144.02, 143.36, 638.2087; (s, 2H), 5.15-5.03 (m, 2H), 142.03,129.31, found, 4.98 (t, J = 9.3 Hz, 1H), 4.04 128.70 (q, J = 32.4638.2109 (dd, J = 11.7, 7.2 Hz, 1H), Hz), 125.44 (q, J = 3.91 (s, 3H),3.63-3.48 (m, 3.7 Hz), 124.22 (q, J = 3H), 2.80 (dd, J = 14.3, 4.3 271.8Hz), 109.75, Hz, 1H), 2.42 (dd, J = 14.2, 89.39, 76.88, 74.07, 10.8 Hz,1H), 2.23-2.10 (m, 72.84, 72.61, 56.21, 1H), 2.06 (s, 3H), 1.65-1.5651.98, 45.67, 35.15, (m, 1H), 1.35 (d, J = 6.3 Hz, 20.86, 18.21, 12.79,3H), 1.07-0.99 (m, 2H), 0.97- 8.77, 8.68 0.86 (m, 2H) F99 — — HRMS-ESI¹H NMR (CDCl₃) δ 8.40 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.2 Hz, 1H), 8.27(d, J = 5.4 171.67, 170.26, [M]⁺ Hz, 1H), 7.55 (d, J = 8.0 Hz, 163.18,160.20, calcd for 2H), 7.31 (d, J = 8.0 Hz, 2H), 145.78, 144.27,C₃₀H₃₇F₃N₂O₉, 6.95 (d, J = 5.4 Hz, 1H), 5.72 143.94, 142.10, 626.2451;(s, 2H), 5.07-4.95 (m, 2H), 129.45, 128.48 (q, J = found 4.03 (dd, J =11.7, 7.3 Hz, 32.1 Hz), 125.37 (q, J = 626.2461 1H), 3.91 (s, 3H),3.53-3.38 3.7 Hz), 124.28 (q, J = (m, 4H), 3.33 (dd, J = 8.3, 6.4 271.8Hz), 109.71, Hz, 1H), 3.23-3.09 (m, 2H), 2.42 89.39, 84.56, 79.48, (dd,J = 13.7, 11.8 Hz, 1H), 75.60, 72.52, 72.01, 2.06 (s, 3H), 2.02-1.94 (m,56.19, 51.83, 47.48, 1H), 1.94-1.82 (m, 1H), 1.50 35.02, 29.19, 20.86,(d, J = 6.4 Hz, 3H), 0.96 19.46, 18.81 (d, J = 6.7 Hz, 6H) F100 — —HRMS-ESI ¹H NMR (CDCl₃) δ 8.38 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.0 Hz,1H), 8.27 (d, J = 5.3 171.77, 170.26, [M]⁺ Hz, 1H), 7.55 (d, J = 8.0 Hz,163.16, 160.20, calcd for 2H), 7.31 (d, J = 8.0 Hz, 2H), 145.77, 144.59,C₃₁H₃₇F₃N₂O₉, 6.95 (d, J = 5.4 Hz, 1H), 5.72 143.94, 142.12, 638.2451;(s, 2H), 5.05-4.92 (m, 2H), 4.16- 129.41, 128.42 (q, J = found, 4.02 (m,2H), 3.91 (s, 3H), 3.43 32.6 Hz), 125.36 (q, J = 638.2472 (qd, J = 11.5,3.9 Hz, 2H), 3.38- 3.7 Hz), 124.29 (q, J = 3.29 (m, 2H), 3.22 (dd, J =13.6, 271.8 Hz) 109.71, 3.5 Hz, 1H), 2.44 (dd, J = 13.6, 89.39, 83.62,83.29, 12.2 Hz, 1H), 2.05 (s, 3H), 1.96- 76.04, 72.90, 72.77, 1.68 (m,7H), 1.61-1.55 (m, 2H), 56.19, 52.07, 47.50, 1.52 (d, J = 6.5 Hz, 3H)35.08, 32.72, 32.62, 23.00, 20.86, 18.91 F101 — — HRMS-ESI ¹H NMR(CDCl₃) δ 8.40 (d, J = ¹⁹F NMR (CDCl₃) (m/z) 8.1 Hz, 1H), 8.27 (d, J =5.4 δ −62.35 [M]⁺ Hz, 1H), 7.59-7.49 (m, 2H), calcd for 7.32 (d, J = 8.0Hz, 2H), 6.95 C₂₉H₃₅F₃N₂O₉ (d, J = 5.4 Hz, 1H), 5.76- 612.2295; 5.69 (m,2H), 5.08-4.95 (m, found, 2H), 4.03 (dd, J = 11.7, 7.3 612.2324 Hz, 1H),3.91 (s, 3H), 3.66 (dt, J = 8.6, 6.6 Hz, 1H), 3.56- 3.37 (m, 4H),3.23-3.13 (m, 2H), 2.42 (dd, J = 13.7, 11.7 Hz, 1H), 2.06 (s, 3H), 2.01-1.89 (m, 1H), 1.69-1.58 (m, 2H), 1.51 (d, J = 6.4 Hz, 3H), 0.97 (t, J =7.4 Hz, 3H) F102 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.42 (d, J = ¹⁹F NMR(CDCl₃) (m/z) 8.1 Hz, 1H), 8.27 (d, J = 5.4 δ −62.43 [M]⁺ Hz, 1H),7.60-7.51 (m, 2H), 7.27 calcd for (d, J = 8.1 Hz, 2H), 6.95C₃₀H₃₅F₃N₂O₁₀, (d, J = 5.4 Hz, 1H), 5.72 640.2244; (d, J = 0.7 Hz, 2H),5.15-5.04 found, (m, 2H), 4.99 (t, J = 9.2 640.2271 Hz, 1H), 4.05 (dd, J= 11.7, 7.2 Hz, 1H), 3.91 (s, 3H), 3.58-3.45 (m, 3H), 2.76 (dd, J =14.2, 3.8 Hz, 1H), 2.58 (hept, J = 7.0 Hz, 1H), 2.40 (dd, J = 14.1, 11.4Hz, 1H), 2.17- 2.07 (m, 1H), 2.06 (s, 3H), 1.35 (d, J = 6.3 Hz, 3H),1.21 (app dd, J = 7.0, 2.8 Hz, 6H) F103 — — HRMS-ESI ¹H NMR (CDCl₃) δ8.40 (d, J = ¹⁹F NMR (CDCl₃) (m/z) 8.2 Hz, 1H), 8.30-8.22 (m, δ −62.34[M]⁺ 1H), 7.55 (dt, J = 8.7, 1.5 calcd for Hz, 2H), 7.32 (d, J = 7.9C₃₁H₃₉F₃N₂O₉, Hz, 2H), 6.94 (d, J = 5.4 Hz, 640.2608; 1H), 5.76-5.68 (m,2H), 5.07- found, 4.93 (m, 2H), 4.03 (dd, J = 640.2636 11.7, 7.3 Hz,1H), 3.91 (s, 3H), 3.69 (dt, J = 8.6, 6.6 Hz, 1H), 3.54 (dt, J = 8.7,6.6 Hz, 1H), 3.50-3.35 (m, 3H), 3.23-3.10 (m, 2H), 2.42 (dd, J = 13.7,11.7 Hz, 1H), 2.06 (s, 3H), 2.01- 1.89 (m, 1H), 1.65-1.56 (m, 2H), 1.51(d, J = 6.4 Hz, 3H), 1.36 (tq, J = 4.9, 2.8, 2.2 Hz, 4H), 0.95-0.86 (m,3H) F104 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.43 (d, J = ¹³C NMR (CDCl₃) δ(m/z) 8.2 Hz, 1H), 8.29 (d, J = 5.3 171.63, 170.27, [M]⁺ Hz, 1H), 6.96(d, J = 5.4 Hz, 163.22, 160.22, calcd for 1H), 5.73 (d, J = 1.2 Hz, 2H),145.80, 143.97, C₂₄H₃₃F₃N₂O₉, 5.08-4.93 (m, 2H), 4.12 (dd, 142.06,127.03 (q, J = 550.2138; J = 11.7, 7.3 Hz, 1H), 3.91 (s, 277.0 Hz),109.75, found, 3H), 3.68 (d, J = 4.0 Hz, 2H), 89.39, 83.18, 78.80,550.2138 3.50 (dd, J = 11.7, 7.5 Hz, 75.48, 72.64, 72.40, 1H), 3.42 (dd,J = 8.4, 6.4 Hz, 56.21, 51.73, 40.04, 1H), 3.20 (dd, J = 8.4, 6.4 Hz,32.64 (q, J = 28.0 Hz), 1H), 3.11 (t, J = 8.8 Hz, 1H), 29.05, 20.87,19.30, 2.48-2.31 (m, 1H), 2.27-2.11 18.86 (m, 1H), 2.11-20.3 (m, 4H),1.92- 1.79 (m, 1H), 1.48 (d, J = 6.4 Hz, 3H), 0.93 (dd, J = 6.6, 1.0 Hz,6H) F105 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.42 (d, J = ¹⁹F NMR (CDCl₃)(m/z) 8.1 Hz, 1H), 8.29 (d, J = 5.3 δ −63.66 [M]⁺ Hz, 1H), 6.96 (d, J =5.4 Hz, 1H), calcd for 5.79-5.69 (m, 2H), 5.06-4.90 C₂₅H₃₃F₃N₂O₉, (m,2H), 4.24-4.13 (m, 1H), 562.2138; 4.03-3.95 (m, 1H), 3.91 (s, 3H),found, 3.75-3.59 (m, 2H), 3.43 (dd, J = 562.2154 11.7, 8.0 Hz, 1 H),3.27 (t, J = 7.8 Hz, 1H), 2.58-2.41 (m, 1H), 2.18-2.09 (m, 1H), 2.07 (s,3H), 2.02-1.93 (m, 1H), 1.82-1.64 (m, 5H), 1.61-1.52 (m, 3H), 1.48 (d, J= 6.5 Hz, 3H) F106 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.49 (d, J = ¹³C NMR(CDCl₃) δ (m/z) 8.0 Hz, 1H), 8.28 (d, J = 5.4 171.53, 170.27, [M]⁺ Hz,1H), 6.95 (d, J = 5.5 Hz, 163.21, 160.20, calcd for 1H), 5.77-5.69 (m,2H), 5.10- 145.79, 143.92, C₂₇H₄₂N₂O₉, 5.00 (m, 1H), 5.00-4.91 (m, 1H),142.21, 109.68, 89.44, 538.2890; 4.06 (dd, J = 11.8, 7.1 Hz, 1H), 84.44,78.86, 75.81, found, 3.91 (s, 3H), 3.70-3.57 (m, 2H), 75.10, 73.08,56.19, 538.2912 3.51 (dd, J = 10.8, 6.6 Hz, 1H), 52.23, 45.79, 36.01,3.34 (dd, J = 8.3, 6.4 Hz, 1H), 3.26 29.14, 28.40, 27.97, (dd, J = 8.3,6.4 Hz, 1H), 3.02 (t, 26.74, 22.76, 22.43, J = 9.2 Hz, 1H), 2.07 (s,3H), 1.84 20.88, 19.49, 18.91 (hept, J = 6.7 Hz, 1H), 1.69- 1.56 (m,2H), 1.48-1.42 (m, 3H), 1.35- 1.23 (m, 2H), 1.18-1.07 (m, 2H), 0.92 (d,J = 6.7 Hz, 6H), 0.88 (app dd, J = 6.6, 3.2 Hz, 6H) F107 — — HRMS-ESI ¹HNMR (CDCl₃) δ 8.48 (d, J = ¹⁹F NMR (CDCl₃) (m/z) 8.1 Hz, 1H), 8.28 (d, J= 5.3 δ −66.42 [M]⁺ Hz, 1H), 6.96 (d, J = 5.4 Hz, calcd for 1H),5.78-5.67 (m, 2H), 5.05 C₂₇H₃₉F₃N₂O₉, (dt, J = 8.1, 6.8 Hz, 1H), 4.94592.2608; (dq, J = 9.0, 6.4 Hz, 1H), 4.06 found, (dd, J = 11.7, 7.1 Hz,1H), 3.91 592.2622 (s, 3H), 3.70-3.48 (m, 5H), 3.06 (t, J = 9.0 Hz, 1H),2.29-2.12 (m, 2H), 2.07 (s, 3H), 1.90-1.79 (m, 2H), 1.66-1.48 (m, 3H),1.44 (d, J = 6.4 Hz, 3H), 1.3 8-1.07 (m, 3H), 0.93-087 (m, 6H) F108 — —HRMS-ESI ¹H NMR (CDCl₃) δ 8.51 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.0 Hz,1H), 8.28 (d, J = 5.3 174.11, 171.42, [M]⁺ Hz, 1H), 6.96 (d, J = 5.4 Hz,170.26, 163.21, calcd for 1H), 5.80-5.67 (m, 2H), 5.15-5.06 160.21,145.78, C₂₇H₃₈N₂O₁₀, (m, 1H), 5.06-4.96 (m, 1H), 143.97, 142.11,550.2526; 4.87 (t, J = 9.5 Hz, 1H), 4.07 109.73, 89.41, 76.51, found,(dd, J = 11.8, 7.1 Hz, 1H), 3.91 75.12, 74.38, 73.31, 550.2536 (s, 3H),3.82-3.65 (m, 2H), 3.59 56.20, 52.32, 44.51, (dd, J = 10.8, 7.2 Hz, 1H),2.07 35.28, 28.18, 27.00, (s, 3H), 1.79-1.69 (m, 1H), 1.69- 22.69,22.16, 20.87, 1.59 (m, 1H), 1.45 (dq, J = 13.0, 18.32, 12.84, 8.48, 6.5Hz, 1H), 1.32 (d, J = 6.3 Hz, 8.38 3H), 1.29-1.19 (m, 2H), 1.17- 1.06(m, 2H), 1.06-0.98 (m, 2H), 0.95-0.89 (m, 2H), 0.89-0.80 (m, 6H) F109 —— HRMS-ESI ¹H NMR (CDCl₃) δ 8.41 (d, J = ¹⁹F NMR (CDCl₃) (m/z) 8.1 Hz,1H), 8.27 (d, J = 5.4 δ −134.79 (dd, J = [M]⁺ Hz, 1H), 6.95 (d, J = 5.4Hz, 20.4, 8.2 Hz), −163.72-−164.43 calcd for 1H), 6.82 (dd, J = 8.3, 6.4Hz, (m) C₂₉H₃₅F₃N₂O₉, 2H), 5.72 (s, 2H), 5.07-4.92 612.2295; (m, 2H),4.05 (dd, J = 11.8, found, 7.3 Hz, 1H), 3.91 (s, 3H), 612.2318 3.52-3.38(m, 4H), 3.30 (dd, J = 8.4, 6.3 Hz, 1H), 3.12 (t, J = 9.0 Hz, 1H), 3.05(dd, J = 13.8, 3.2 Hz, 1H), 2.32 (dd, J = 13.8, 11.8 Hz, 1H), 2.06 (s,3H), 1.93-1.81 (m, 2H), 1.49 (d, J = 6.4 Hz, 3H), 0.95 (dd, J = 6.6, 1.3Hz, 6H) F110 62-66 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.40 (d, J = ¹³C NMR(CDCl₃) δ (m/z) 8.1 Hz, 1H), 8.27 (d, J = 5.4 176.31, 171.68, [M]⁺ Hz,1H), 7.36 (d, J = 2.0 Hz, 163.18, 160.24, calcd for 1H), 7.24-7.07 (m,2H), 6.95 145.76, 135.22, C₂₉H₃₄Cl₂N₂O₁₀, (d, J = 5.4 Hz, 1H), 5.73-134.90, 132.95, 640.1591; 5.69 (m, 2H), 5.19-4.90 (m, 132.40, 129.50,found, 3H), 4.09 (dd, J = 11.7, 7.3 127.12, 109.74, 89.42, 640.1594 Hz,1H), 3.91 (s, 3H), 3.63- 73.97, 72.50, 71.41, 3.33 (m, 3H), 2.78 (d, J =56.21, 51.81, 44.03, 3.6 Hz, 1H), 2.61 (p, J = 7.0 34.24, 32.37, 20.88,Hz, 1H), 2.48 (dd, J = 13.8, 19.05, 18.98, 18.19 12.0 Hz, 1H), 2.17-2.11(m, 1H), 2.06 (s, 3H), 1.35 (d, J = 6.3 Hz, 3H), 1.22 (d, J = 7.6 Hz,6H) F111 49-53 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.40 (d, J = ¹³C NMR (CDCl₃)δ (m/z) 8.1 Hz, 1H), 8.27 (d, J = 5.4 171.63, 170.25, [M]⁺ Hz, 1H), 7.36(s, 1H), 7.27- 163.19, 160.20, calcd for 7.12 (m, 2H), 6.95 (d, J = 5.4145.78, 143.92, C₂₉H₃₆Cl₂N₂O₉, Hz, 1H), 5.72 (s, 2H), 5.08- 142.12,136.19, 626.1798; 4.97 (m, 2H), 4.05 (dd, J = 135.03, 132.52, found,11.7, 7.3 Hz, 1H), 3.90 (s, 3H), 132.15, 129.32, 626.1804 3.55-3.28 (m,5H), 3.28-3.04 127.07, 109.72, 89.39, (m, 2H), 2.66-2.43 84.94, 79.75,75.65, (m, 1H), 2.06 (s, 3H), 1.98- 72.55, 72.01, 56.20, 1.76 (m, 2H),1.50 (d, J = 6.4 51.89, 45.91, 32.13, Hz, 3H), 0.95 (d, J = 6.7 Hz,29.17, 20.86, 19.49, 6H) 18.77 F112 53-57 — HRMS-ESI ¹H NMR (CDCl₃) δ8.41 (d, J = 8.0 ¹³C NMR (CDCl₃) δ (m/z) Hz, 1H), 8.26 (d, J = 5.4171.65, 170.23, [M]⁺ Hz, 1H), 7.36 (s, 1H), 7.25-7.06 163.18, 160.20,calcd for (m, 2H), 6.95 (d, J = 5.4 Hz, 145.78, 143.92, C₃₀H₃₈Cl₂N₂O₉,1H), 5.72 (s, 2H), 5.12-4.85 142.10, 136.17, 640.1954; (m, 2H), 4.05(dd, J = 11.7, 135.03, 132.52, found, 7.3 Hz, 1H), 3.90 (s, 3H), 3.75-132.13, 129.33, 640.1962 3.64 (m, 1H), 3.62-3.52 (m, 1H), 127.06,109.73, 89.37, 3.47-3.38 (m, 3H), 3.26-3.08 85.22, 75.63, 73.28, (m,2H), 2.63-2.43 (m, 1H), 2.13- 72.52, 71.95, 56.20, 1.97 (m, 1H), 2.06(s, 3H), 1.69- 51.86, 45.87, 32.20, 1.54 (m, 2H), 1.50 (d, J = 6.4 Hz,29.96, 28.32, 22.57, 3H), 1.38-1.31 (m, 4H), 0.90 20.86, 18.72, 14.01(t, J = 7.2 Hz, 3H) F113 70-74 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.42 (d, J =¹³C NMR (CDCl₃) δ (m/z) 8.1 Hz, 1H), 8.27 (d, J = 5.4 171.73, 170.26,[M]⁺ Hz, 1H), 7.32 (s, 1H), 7.15 (s, 163.21, 160.23, calcd for 2H), 7.10(d, J = 8.4 Hz, 2H), 156.98, 145.80, C₃₂H₃₄Cl₂N₂O₉, 6.95 (d, J = 5.4 Hz,1H), 6.88 143.97, 142.05, 660.1641; (d, J = 8.5 Hz, 2H), 5.73 (s,135.80, 134.96, found, 2H), 5.16 (dd, J = 8.9, 6.5 Hz, 132.65, 132.24,660.1647 1H), 5.07 (q, J = 7.6 Hz, 1H), 130.64, 130.18, 4.30 (t, J = 8.8Hz, 1H), 4.12 129.36, 127.02, (dd, J = 11.6, 7.4 Hz, 1H), 115.14,109.78, 89.38, 3.95-3.87 (m, 1H), 3.90 (s, 81.97, 75.40, 72.37, 3H),3.62-3.35 (m, 3H), 3.05 71.38, 56.22, 51.77, (dd, J = 13.7, 3.4 Hz, 1H),46.12, 32.42, 20.88, 2.57-2.46 (m, 1H), 2.29 (s, 20.44, 18.94 3H), 2.07(s, 3H), 1.41 (d, J = 6.4 Hz, 3H) F114 41-45 — HRMS-ESI ¹H NMR (CDCl₃) δ8.47 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.0 Hz, 1H), 8.28 (d, J = 5.4176.19, 171.63, [M]⁺ Hz, 1H), 6.96 (d, J = 5.4 Hz, 170.26, 163.19, calcdfor 1H), 5.78-5.68 (m, 2H), 5.11 160.22, 145.77, C₂₈H₄₀N₂O₁₀, (q, J =7.1 Hz, 1H), 5.02 (dd, J = 144.00, 142.10, 564.2683; 9.3, 6.4 Hz, 1H),4.80 (t, J = 109.73, 89.42, 74.33, found, 9.3 Hz, 1H), 4.10 (dd, J =73.88, 72.77, 56.20, 564.2687 11.7, 7.3 Hz, 1H), 3.91 (s, 52.05, 43.59,37.20, 3H), 3.73 (d, J = 9.7 Hz, 1H), 35.04, 34.26, 33.63, 3.67-3.53 (m,2H), 2.59 32.13, 25.02, 20.86, (hept, J = 6.7 Hz, 1H), 2.07 (s, 18.97,18.33 3H), 1.93-1.67 (m, 4H), 1.59- 1.48 (m, 4H), 1.31 (d, J = 6.4 Hz,3H), 1.20 (d, J = 7.0 Hz, 6H), 1.14-0.91 (m, 4H) F115 — — HRMS-ESI ¹HNMR (CDCl₃) δ 8.46 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.0 Hz, 1H), 8.28 (d,J = 5.4 171.69, 170.25, [M]⁺ Hz, 1H), 6.95 (d, J = 5.4 Hz, 163.18,160.20, calcd for 1H), 5.77-5.69 (m, 2H), 5.03 145.78, 142.23,C₂₈H₄₂N₂O₉, (q, J = 7.1 Hz, 1H), 4.95 (dd, J = 137.51, 131.24, 550.2890;9.1, 6.4 Hz, 1H), 4.08 (dd, J = 109.69, 89.43, 84.91, found, 11.7, 7.2Hz, 1H), 3.91 (s, 3H), 74.23, 72.74, 56.19, 550.2877 3.63 (d, J = 10.6Hz, 1H), 3.59- 52.07, 44.74, 37.39, 3.48 (m, 2H), 3.37 (dd, J = 8.3,34.97, 33.88, 32.02, 6.2 Hz, 1H), 3.24 (dd, J = 8.2, 29.14, 25.09,20.87, 6.7 Hz, 1H), 2.97 (t, J = 9.0 Hz, 19.53, 18.86 1H), 2.07 (s, 3H),1.93-1.70 (m, 4H), 1.70-1.48 (m, 6H), 1.45 (d, J = 6.4 Hz, 3H),1.16-1.02 (m, 3H), 0.92 (dd, J = 6.7, 4.5 Hz, 6H) F116 — — HRMS-ESI ¹HNMR (CDCl₃) δ 8.46 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.1 Hz, 1H), 8.28 (d,J = 5.4 171.68, 170.24, [M]⁺ Hz, 1H), 6.96 (d, J = 5.4 Hz, 163.18,160.19, calcd for 1H), 5.76-5.69 (m, 2H), 5.03 145.78, 143.91,C₂₉H₄₄N₂O₉, (q, J = 7.1 Hz, 1H), 4.94 (dd, J = 142.19, 109.70, 89.40,564.3047; 9.1, 6.4 Hz, 1H), 4.08 (dd, J = 85.24, 75.84, 74.23, found,11.7, 7.2 Hz, 1H), 3.91 (s, 72.72, 56.19, 52.04, 564.3059 3H), 3.67-3.42(m, 5H), 2.98 44.72, 37.38, 35.10, (t, J = 9.0 Hz, 1H), 2.07 (s, 33.85,32.04, 29.94, 3H), 1.94-1.84 (m, 2H), 1.82- 28.36, 25.08, 22.55, 1.70(m, 2H), 1.68-1.48 (m, 7H), 20.86, 18.81, 14.00 1.46 (d, J = 6.4 Hz,3H), 1.39-1.21 (m, 5H), 1.17-1.01 (m, 2H), 0.94-0.86 (m, 3H) F117 — —HRMS-ESI ¹H NMR (CDCl₃) δ 8.39 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.1 Hz,1H), 8.26 (d, J = 5.4 171.78, 170.26, [M + Na]⁺ Hz, 1H), 7.09 (m, 4H),6.94 163.15, 160.18, calcd for (d, J = 5.4 Hz, 1H), 5.72 145.76, 143.91,C₃₀H₄₀N₂O₉Na, (s, 2H), 5.00 (m, 2H), 4.01 (dd, J = 142.14, 136.82,595.2626; 11.6, 7.4 Hz, 1H), 3.90 (s, 3H), 135.53, 129.11, found, 3.41(m, 5H), 3.12 (m, 2H), 2.31 129.05, 109.68, 89.40, 595.2620 (s, 3H),2.26 (d, J = 13.4 Hz, 84.58, 79.17, 75.72, 1H), 2.05 (s, 3H), 1.8972.33, 72.26, 56.18, (dd, J = 13.3, 6.6 Hz, 2H), 51.82, 47.44, 34.61,1.49 (d, J = 6.4 Hz, 3H), 29.18, 21.01, 20.87, 0.96 (d, J = 6.7 Hz, 6H)19.49, 18.84 F118 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.56 (d, J = ¹³C NMR(CDCl₃) δ (m/z) 8.0 Hz, 1H), 8.28 (d, J = 5.4 176.26, 174.16, [M]⁺ Hz,1H), 7.32-7.24 (m, 2H), 171.45, 163.19, calcd for 7.23-7.10 (m, 3H),6.95 (d, J = 160.22, 145.65, C₃₂H₄₀N₂O₁₀, 5.4 Hz, 1H), 5.8 1-5.72 (m,144.23, 141.77, 612.2683; 2H), 5.18-5.08 (m, 1H), 5.08- 128.39, 128.32,found, 4.98 (m, 1H), 4.94 (t, J = 9.3 125.92, 109.68, 89.78, 612.2705Hz, 1H), 4.17-4.06 (m, 1H), 76.27, 74.47, 74.32, 3.90 (s, 3H), 3.88-3.80(m, 73.16, 56.16, 52.17, 1H), 3.74-3.62 (m, 2H), 2.79- 43.88, 33.86,32.47, 2.65 (m, 1H), 2.60-2.43 31.32, 18.68, 18.30, (m, 2H), 1.90-1.79(m, 1H), 12.87, 8.54 1.66-1.58 (m, 2H), 1.56- 1.45 (m, 1H), 1.33 (d, J =6.2 Hz, 3H), 1.15 (d, J = 7.0 Hz, 6H), 1.04-0.97 (m, 2H), 0.94-0.86 (m,2H) F119 57-60 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.46 (d, J = — (m/z) 8.1 Hz,1H), 8.26 (d, J = 5.3 [M]⁺ Hz, 1H), 7.36 (d, J = 1.9 Hz, calcd for 1H),7.25-7.07 (m, 2H), 6.94 C₃₁H₃₈Cl₂N₂O₁₀, (d, J = 5.4 Hz, 1H), 5.84-668.1904; 5.70 (m, 2H), 5.18-4.86 (m, found, 3H), 4.09 (dd, J = 11.6,7.4 668.1908 Hz, 1H), 3.89 (s, 3H), 3.62- 3.32 (m, 3H), 2.80 (dd, J =13.9, 3.6 Hz, 1H), 2.70-2.39 (m, 3H), 2.27-2.08 (m, 1H), 1.35 (d, J =6.3 Hz, 3H), 1.23 (d, J = 7.0 Hz, 6H), 1.14 (d, J = 7.0 Hz, 6H) F120 — —HRMS-ESI ¹H NMR (CDCl₃) δ 8.41 (d, J = ¹⁹F NMR (CDCl₃) (m/z) 8.2 Hz,1H), 8.26 (d, J = 5.4 δ −62.35 [M]⁺ Hz, 1H), 7.61-7.50 (m, 2H), calcdfor 7.32 (d, J = 8.0 Hz, 2H), 6.95 C₃₁H₃₉F₃N₂O₁₀, (d, J = 5.4 Hz, 1H),5.80 (s, 656.2557; 2H), 5.04-4.95 (m, 2H), 4.08 (s, found, 2H), 4.03(dd, J = 11.7, 7.3 Hz, 656.2569 1H), 3.90 (s, 3H), 3.66 (dt, J = 8.6,6.6 Hz, 1H), 3.63-3.47 (m, 3H), 3.47-3.36 (m, 3H), 3.23-3.12 (m, 2H),2.43 (dd, J = 13.7, 11.7 Hz, 1H), 2.01-1.90 (m, 1H), 1.69- 1.58 (m, 2H),1.51 (d, J = 6.4 Hz, 3H), 1.22 (t, J = 7.0 Hz, 3H), 0.97 (t, J = 7.4 Hz,3H) F121 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.48 (d, J = ¹³C NMR (CDCl₃) δ(m/z) 8.1 Hz, 1H), 8.28 (d, J = 5.4 176.17, 171.61, [M]⁺ Hz, 1H), 6.97(d, J = 5.4 Hz, 170.04, 163.14, calcd for 1H), 5.81 (s, 2H), 5.12-4.98160.13, 145.81, C₃₀H₄₄N₂O₁₁, (m, 2H), 4.81 (t, J = 9.3 Hz, 143.93,141.93, 608.2945; 1H), 4.10 (s, 3H), 3.91 (s, 3H), 109.84, 89.39, 74.31,found, 3.76-3.56 (m, 6H), 2.58 (h, J = 73.85, 72.71, 67.77, 608.2950 7.0Hz, 1H), 1.93-1.68 (m, 67.17, 56.23, 52.01, 4H), 1.62-1.46 (m, 4H), 1.3143.55, 37.19, 35.02, (d, J = 6.4 Hz, 3H), 1.25- 34.25, 33.61, 32.12,1.17 (m, 9H), 1.12-0.94 (m, 25.00, 19.02, 18.31, 3H) 14.99 F122 — —HRMS-ESI ¹H NMR (CDCl₃) δ 8.42 (d, J = ¹³C NMR (CDCl₃) δ (m/z) 8.1 Hz,1H), 8.26 (d, J = 5.4 171.62, 170.01, [M]⁺ Hz, 1H), 7.36 (s, 1H), 7.26-163.12, 160.10, calcd for 7.12 (m, 2H), 6.95 (d, J = 5.4 145.82, 143.86,C₃₂H₄₂Cl₂N₂O₁₀, Hz, 1H), 5.80 (s, 2H), 5.08- 141.95, 136.17, 684.2217;4.91 (m, 2H), 4.09 (s, 2H), 135.01, 132.51, found, 4.05 (dd, J = 11.7,7.3 Hz, 132.13, 129.31, 684.2232 1H), 3.90 (s, 3H), 3.76-3.64 127.05,109.83, 89.36, (m, 1H), 3.63-3.54 (m, 3H), 85.20, 75.62, 73.28,3.46-3.38 (m, 3H), 3.22- 72.49, 71.95, 67.77, 3.13 (m, 2H), 2.56 (dd, J= 67.16, 56.23, 51.83, 13.6, 12.2 Hz, 1H), 2.08- 45.85, 32.19, 29.95,1.95 (m, 1H), 1.65-1.56 (m, 28.31, 22.56, 18.71, 2H), 1.50 (d, J = 6.4Hz, 3H), 15.00, 14.00 1.38-1.31 (m, 3H), 1.28- 1.2 1 (m, 4H), 0.90 (t, J= 7.1 Hz, 3H) F123 96-99 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.55 (d, J = ¹³CNMR (CDCl₃) δ (m/z) 7.7 Hz, 1H), 8.31 (d, J = 5.4 171.57, 169.34, [M]⁺Hz, 1H), 7.36 (s, 1H), 7.25- 162.64, 159.42, calcd for 7.12 (m, 2H),6.99 (d, J = 5.5 146.81, 141.13, C₃₁H₄₀Cl₂N₂O₉, Hz, 1H), 5.08-4.89 (m,2H), 137.35, 136.16, 654.2111; 4.02 (dd, J = 11.7, 7.3 Hz, 135.02,132.53, found, 1H), 3.88 (s, 3H), 3.81 (t, J = 132.12, 129.33, 654.21416.6 Hz, 2H), 3.72-3.61 (m, 127.07, 109.93, 85.20, 2H), 3.61-3.49 (m,1H), 3.46- 75.61, 73.24, 72.45, 3.32 (m, 3H), 3.41 (s, 3H), 71.84,67.56, 58.77, 3.20-3.08 (m, 2H), 2.97 (t, J = 56.33, 51.58, 34.60, 6.6Hz, 2H), 2.59-2.48 (m, 32.19, 29.96, 28.32, 1H), 2.05-1.95 (m, 1H),1.65- 22.57, 18.71, 14.01 1.54 (m, 2H), 1.49 (d, J = 6.4 Hz, 3H),1.38-1.31 (m, 3H), 0.90 (t, J = 7.1 Hz, 3H) F124 — — ESIMS ¹H NMR(CDCl₃) δ 7.31- ¹³C NMR (CDCl₃) δ m/z 584 7.23 (m, 2H), 7.21-7.12 (m,169.88, 152.65, ([M + Na]⁺) 3H), 5.06 (app t, J = 7.4 Hz, 128.35,128.30, 1H), 4.84 (dq, J = 8.3, 6.5 Hz, 125.75, 83.13, 82.95, 1H), 4.19(dd, J = 11.8, 7.3 82.77, 75.93, 75.32, Hz, 1H), 4.04-3.91 (m, 2H),71.84, 57.87, 45.13, 3.66 (d, J = 4.1 Hz, 2H), 3.22 34.03, 32.59, 32.54,(app t, J = 7.7 Hz, 1H), 2.76 30.65, 27.97, 27.94, (ddd, J = 13.6, 10.8,4.8 Hz, 23.06, 23.04, 19.10 1H), 2.59 (ddd, J = 13.7, 10.3, 6.1 Hz, 1H),2.04-1.92 (m, 1H), 1.77-1.46 (m, 28H), 1.43 (d, J = 6.5 Hz, 3H) F125 — —ESIMS ¹H NMR (CDCl₃) δ 7.32- ¹⁹F NMR (CDCl₃) m/z 626 7.23 (m, 2H),7.23-7.13 (m, δ −66.40 ([M + Na]⁺) 3H), 5.15 (dd, J = 8.4, 6.1 Hz, 1H),4.91-4.79 (m, 1H), 4.23 (dd, J = 11.9, 6.2 Hz, 1H), 3.94 (dd, J = 11.9,8.5 Hz, 1H), 3.73 (dd, J = 10.9, 1.6 Hz, 1H), 3.61 (dd, J = 11.0, 6.2Hz, 1H), 3.57-3.41 (m, 2H), 3.10 (app t, J = 8.6 Hz, 1H), 2.78 (ddd, J =13.8, 10.3, 4.8 Hz, 1H), 2.59-2.49 (m, 1H), 2.20-2.07 (m, 2H), 1.89-1.71 (m, 4H), 1.61-1.49 (m, 19H), 1.41 (d, J = 6.4 Hz, 3H) F126 — —ESIMS ¹H NMR (CDCl₃) δ 7.31- ¹³C NMR (CDCl₃) δ m/z 586 7.22 (m, 2H),7.21-7.12 (m, 169.70, 152.67, ([M + Na]⁺) 3H), 5.16 (dd, J = 8.5, 5.8Hz, 142.28, 128.36, 1H), 4.84 (dq, J = 9.0, 6.3 Hz, 128.34, 125.79,84.57, 1H), 4.22 (dd, J = 11.9, 5.8 82.96, 75.41, 75.21, Hz, 1H), 3.93(dd, J = 11.9, 71.87, 71.68, 57.77, 8.5 Hz, 1H), 3.76 (dd, J = 44.75,33.31, 31.00, 10.9, 1.6 Hz, 1H), 3.56 (dd, J = 29.97, 28.38, 27.95,10.9, 6.4 Hz, 1H), 3.53- 22.59, 18.98, 14.02 3.37 (m, 2H), 3.07 (app t,J = 8.9 Hz, 1H), 2.76 (ddd, J = 13.6, 10.9, 4.7 Hz, 1H), 2.55 (ddd, J =13.7, 10.4, 6.3 Hz, 1H), 1.93 (dddd, J = 13.9, 10.9, 6.4, 3.2 Hz, 1H),1.79- 1.67 (m, 1H), 1.51 (s, 21H), 1.43 (d, J = 6.3 Hz, 3H), 1.35-1.23(m, 4H), 0.96-0.82 (m, 3H) F127 — — ESIMS ¹H NMR (CDCl₃) δ 7.31- ¹³C NMR(CDCl₃) δ m/z 573 7.22 (m, 2H), 7.21-7.13 (m, 169.71, 152.68, ([M +Na]⁺) 3H), 5.16 (dd, J = 8.5, 5.8 Hz, 142.27, 128.36, 1H), 4.90-4.81 (m,1H), 4.22 125.79, 84.24, 82.95, (dd, J = 11.9, 5.9 Hz, 1H), 78.20,75.35, 75.13, 3.93 (dd, J = 11.9, 8.5 Hz, 71.68, 57.77, 44.70, 1H),3.80-3.72 (m, 1H), 3.57 33.31, 30.87, 29.08, (dd, J = 10.9, 6.4 Hz, 1H),27.95, 19.46, 19.44, 3.30-3.16 (m, 2H), 3.07 (app 19.03 t, J = 8.9 Hz,1H), 2.84-2.67 (m, 1H), 2.61-2.45 (m, 1H), 1.93 (dddd, J = 13.8, 11.0,6.5, 3.2 Hz, 1H), 1.85-1.68 (m, 2H), 1.54-1.49 (m, 19H), 1.43 (d, J =6.4 Hz, 3H), 0.89 (d, J = 6.7 Hz, 6H) F128 130-132 — ESIMS ¹H NMR(CDCl₃) δ 8.01- — m/z 622 7.93 (m, 1H), 7.84 (dd, J = ([M + Na]⁺) 8.0,1.5 Hz, 1H), 7.72 (d, J = 8.1 Hz, 1H), 7.54-7.41 (m, 2H), 7.37 (dd, J =8.2, 7.0 Hz, 1H), 7.28 (dd, J = 7.0, 1.3 Hz, 1H), 5.20 (dd, J = 8.7, 5.7Hz, 1H), 5.11 (app t, J = 9.3 Hz, 1H), 5.08-4.97 (m, 1H), 4.06 (dd, J =11.8, 5.7 Hz, 1H), 3.86 (dd, J = 11.9, 8.7 Hz, 1H), 3.66 (d, J = 11.0Hz, 1H), 3.50 (dd, J = 10.8, 6.4 Hz, 1H), 3.23 (dd, J = 14.0, 3.1 Hz,1H), 2.74-2.55 (m, 2H), 2.37-2.20 (m, 1H), 1.42 (s, 18H), 1.37 (d, J =6.2 Hz, 3H), 1.26 (app dd, J = 7.0, 4.4 Hz, 6H) F129 — — ESIMS ¹H NMR(CDCl₃) δ 8.13-8.06 ¹⁹F NMR (CDCl₃) m/z 662 (m, 1H), 7.84 (dd, J = δ−66.36 ([M + Na]⁺) 7.8, 1.7 Hz, 1H), 7.72 (dd, J = 8.1, 1.3 Hz, 1H),7.54-7.41 (m, 2H), 7.38 (dd, J = 8.1, 6.9 Hz, 1H), 7.32 (dd, J = 7.1,1.4 Hz, 1H), 5.12 (dd, J = 8.5, 6.8 Hz, 1 H), 4.87 (dq, J = 9.0, 6.4 Hz,1H), 4.04 (dd, J = 11.7, 6.8 Hz, 1H), 3.88 (dd, J = 11.7, 8.6 Hz, 1H),3.84-3.76 (m, 1H), 3.77-3.66 (m, 1H), 3.56 (dd, J = 13.5, 3.0 Hz, 1H),3.48-3.41 (m, 2H), 3.28 (app t, J = 8.9 Hz, 1H), 2.76 (app t, J = 12.4Hz, 1H), 2.34- 2.22 (m, 2H), 2.15-2.04 (m, 1H), 2.00-1.86 (m, 2H), 1.51(d, J = 6.4 Hz, 3H), 1.43 (s, 18H) F130 — IR: ESIMS ¹H NMR (CDCl₃) δ8.21- — 2932, 2873, m/z 622 8.13 (m, 1H), 7.87-7.79 1743, 1707, ([M +H]⁺) (m, 1H), 7.71 (dd, J = 8.0, 1.3 Hz, 1356, 1121 1H), 7.54-7.41 (m,2H), 7.42- 7.28 (m, 2H), 5.12 (dd, J = 8.6, 6.7 Hz, 1H), 4.85 (dq, J =9.2, 6.3 Hz, 1H), 4.03 (dd, J = 11.7, 6.7 Hz, 1H), 3.92-3.73 (m, 2H),3.73-3.63 (m, 2H), 3.51-3.37 (m, 2H), 3.24 (app t, J = 9.1 Hz, 1H),2.78-2.65 (m, 1H), 2.13-2.02 (m, 1H), 1.77-1.64 (m, 2H), 1.57- 1.49 (m,4H), 1.42 (m, 21H), 0.91 (t, J = 7.1 Hz, 3H) F131 — — ESIMS ¹H NMR(CDCl₃) δ 8.11- ¹³C NMR (CDCl₃) δ m/z 642 8.03 (m, 1H), 7.81 (dd, J =169.99, 157.28, ([M + Na]⁺) 7.9, 1.6 Hz, 1H), 7.69 (d, J = 152.59,135.48, 8.1 Hz, 1H), 7.54-7.39 (m, 133.98, 131.99, 2H), 7.39-7.30 (m,1H), 7.27 130.55, 130.22, (dd, J = 7.0, 1.4 Hz, 1H), 7.16- 128.67,127.79, 7.08 (m, 2H), 7.03-6.95 127.09, 125.91, (m, 2H), 5.17 (dd, J =8.7, 6.5 125.43, 125.14, Hz, 1H), 5.09-4.99 (m, 1H), 124.04, 115.18,83.05, 4.40 (app t, J = 9.0 Hz, 1H), 82.23, 75.40, 72.08, 4.08 (dd, J =11.7, 6.6 Hz, 70.65, 57.24, 46.50, 1H), 3.91 (dd, J = 11.7, 8.7 32.68,27.84, 20.43, Hz, 1H), 3.63-3.48 (m, 3H), 19.10 2.69-2.64 (m, 1H), 2.37-2.26 (m, 4H), 1.47-1.38 (m, 21H) F132 49-55 — ESIMS ¹H NMR (CDCl₃) δ8.09 (d, J = — m/z 620 8.3 Hz, 1H), 7.82 (dd, J = ([M + Na]⁺) 8.1, 1.5Hz, 1H), 7.74-7.67 (m, 1H), 7.54-7.41 (m, 2H), 7.40-7.31 (m, 2H), 5.05(app t, J = 7.7 Hz, 1H), 4.90-4.79 (m, 1H), 4.21-4.12 (m, 1H), 3.94 (dd,J = 11.7, 7.5 Hz, 1H), 3.88 (dd, J = 11.7, 8.0 Hz, 1H), 3.73 (dd, J =13.6, 2.9 Hz, 1H), 3.53-3.35 (m, 3H), 2.71 (app t, J = 12.8 Hz, 1H),2.07-1.96 (m, 1H), 1.90- 1.70 (m, 6H), 1.63-1.49 (m, 5H), 1.38 (s, 18H)F133 57-63 — ESIMS ¹H NMR (CDCl₃) δ 8.17 (dd, J = — m/z 608 8.0, 1.6 Hz,1H), 7.82 (dd, J = ([M + Na]⁺) 7.7, 1.8 Hz, 1H), 7.71 (d, J = 8.0 Hz,1H), 7.51-7.40 (m, 2H), 7.37 (dd, J = 8.1, 6.9 Hz, 1H), 7.32 (dd, J =7.0, 1.4 Hz, 1H), 5.12 (dd, J = 8.6, 6.5 Hz, 1H), 4.93-4.83 (m, 1H),4.02 (dd, J = 11.7, 6.5 Hz, 1H), 3.86 (dd, J = 11.8, 8.6 Hz, 1H), 3.68(dd, J = 13.6, 2.8 Hz, 1H), 3.59-3.36 (m, 4H), 3.23 (app t, J = 9.1 Hz,1H), 2.74-2.63 (m, 1H), 2.14- 2.05 (m, 1H), 2.05-1.94 (m, 1H), 1.53 (d,J = 6.4 Hz, 3H), 1.41 (s, 18H), 1.01 (app dd, J = 6.7, 2.1 Hz, 6H) F134100-103 — ESIMS ¹H NMR (CDCl₃) δ 7.08 (app — m/z 586 s, 4H), 5.12 (dd, J= 8.6, 6.3 ([M + Na]⁺) Hz, 1H), 4.91-4.81 (m, 1H), 4.07 (dd, J = 11.8,6.3 Hz, 1H), 3.83 (dd, J = 11.8, 8.6 Hz, 1H), 3.68-3.58 (m, 1H),3.57-3.45 (m, 2H), 3.36 (dd, J = 10.9, 6.2 Hz, 1H), 3.18- 3.02 (m, 2H),2.37-2.26 (m, 4H), 2.00-1.89 (m, 1H), 1.64- 1.55 (m, 2H), 1.51-1.44 (m,21H), 1.39-1.27 (m, 4H), 0.94-0.85 (m, 3H) F135 — — ESIMS ¹H NMR (CDCl₃)δ 7.07 (d, J = ¹³C NMR (CDCl₃) δ m/z 586 7.9 Hz, 2H), 7.01 (d, J = 8.1176.14, 169.82, ([M + Na]⁺) Hz, 2H), 5.19 (dd, J = 8.7, 5.8 152.55,135.97, Hz, 1H), 5.02-4.90 (m, 2H), 135.63, 129.08, 4.12 (dd, J = 11.9,5.8 Hz, 128.92, 82.95, 76.78, 1H), 3.86 (dd, J = 11.9, 8.7 73.88, 73.23,71.24, Hz, 1H), 3.64 (d, J = 10.6 Hz, 57.60, 45.58, 34.43, 1H), 3.45(dd, J = 10.8, 6.7 34.15, 27.89, 20.96, Hz, 1H), 2.67 (dd, J = 13.9,18.97, 18.95, 18.38 3.7 Hz, 1H), 2.61-2.51 (m, 1H), 2.32-2.20 (m, 4H),2.16- 2.04 (m, 1H), 1.49 (s, 18H), 1.32 (d, J = 5.5 Hz, 3H), 1.19 (appdd, J = 7.0, 1.5 Hz, 6H) F136 131-133 — ESIMS ¹H NMR (CDCl₃) δ 7.15- —m/z 588 7.04 (m, 2H), 7.01-6.92 (m, ([M + Na]⁺) 2H), 5.19 (dd, J = 8.7,5.6 Hz, 1H), 5.02-4.89 (m, 2H), 4.13 (dd, J = 11.9, 5.7 Hz, 1H), 3.87(dd, J = 11.9, 8.7 Hz, 1H), 3.64 (d, J = 10.8 Hz, 1H), 3.44 (dd, J =10.9, 6.7 Hz, 1H), 2.71 (dd, J = 14.1, 4.1 Hz, 1H), 2.30 (dd, J = 14.2,10.8 Hz, 1H), 2.17-2.03 (m, 1H), 1.66-1.57 (m, 1H), 1.49 (s, 18H), 1.33(d, J = 5.6 Hz, 3H), 1.06-0.96 (m, 2H), 0.95- 0.85 (m, 2H) F137 — —ESIMS ¹H NMR (CDCl₃) δ 7.13- ¹³C NMR (CDCl₃) δ m/z 590 7.05 (m, 2H),7.00-6.91 (m, 176.22, 169.76, ([M + Na]⁺) 2H), 5.18 (dd, J = 8.7, 5.7Hz, 161.45 (d, JCF = 1H), 5.02-4.89 (m, 2H), 4.13 (dd, 244.4 Hz),152.60, J = 11.9, 5.8 Hz, 1H), 3.87 134.77 (d, JCF = (dd, J = 11.9, 8.6Hz, 1H), 3.3 Hz), 130.45 (d, 3.62 (d, J = 10.8 Hz, 1H), 3.45 JCF = 7.8Hz), 115.21 (dd, J = 10.9, 6.6 Hz, 1H), 2.66 (d, JCF = 21.1 Hz), (dd, J= 14.0, 3.8 Hz, 1H), 2.57 83.07, 76.72, 73.81, (app p, J = 7.0 Hz, 1H),2.29 73.08, 71.36, 57.58, (dd, J = 14.1, 11.1 Hz, 1H), 45.72, 34.18,34.11, 2.11-2.01 (m, 1H), 1.49 (s, 27.91, 18.99, 18.96, 18H), 1.32 (d, J= 5.6 Hz, 18.38 3H), 1.20 (app dd, J = 7.0, 1.8 Hz, 6H) F138 — — ESIMS¹H NMR (CDCl₃) δ 7.30- ¹³C NMR (CDCl₃) δ m/z 585 7.23 (m, 2H), 7.20-7.14(m, 174.15, 169.50, ([M + Na]⁺) 1H), 7.14-7.10 (m, 2H), 5.23 152.65,141.92, (dd, J = 8.8, 5.0 Hz, 1H), 4.97- 129.08, 128.37, 4.88 (m, 2H),4.26 (dd, J = 128.29, 125.87, 12.0, 5.0 Hz, 1H), 3.95 (dd, J = 83.08,76.37, 74.11, 12.0, 8.8 Hz, 1H), 3.89 (dd, J = 72.11, 57.93, 43.64,10.8, 1.3 Hz, 1H), 3.61 (dd, J = 32.43, 31.39, 27.96, 10.8, 7.2 Hz, 1H),2.74-2.63 18.41, 12.90, 8.50 (m, 1H), 2.51-2.40 (m, 1H), 1.88 (q, J =9.2, 8.0 Hz, 1H), 1.66- 1.45 (m, 21H), 1.30 (d, J = 5.8 Hz, 3H),1.03-0.97 (m, 2H), 0.93- 0.85 (m, 2H) F139 — (Thin Film) HRMS-ESI ¹H NMR(CDCl₃) δ 7.23- — 2979, 2921, (m/z) 7.16 (m, 2H), 7.16-7.09 (m, 1742,1705, [M]⁺ 1H), 7.09-7.03 (m, 2H), 7.01- 1507, 1355, calcd for 6.96 (m,2H), 6.83-6.78 1234, 1169, C₃₃H₄₅NO₈, (m, 2H), 5.20 (dd, J = 8.5, 5.91143, 1120 583.3145; Hz, 1H), 5.05-4.94 (m, 1H), found, 1.89-1.77 (m,1H), 4.27 (dd, 583.3159 J = 11.9, 6.0 Hz, 1H), 4.20 (t, J = 8.8 Hz, 1H),4.04-3.94 (m, 1H), 3.83 (d, J = 10.8 Hz, 1H), 3.72-3.63 (m, 1H), 2.70-2.60 (m, 1H), 2.57-2.44 (m, 1H), 2.28 (s, 3H), 2.00- 1.90 (m, 1H),1.56-1.48 (m, 19H), 1.35 (d, J = 6.5 Hz, 3H) F140 — — ESIMS ¹H NMR(CDCl₃) δ 7.17- ¹³C NMR (CDCl₃) δ m/z 631 7.09 (m, 2H), 7.02-6.91 (m,169.88, 161.42 (d, J = ([M + Na]⁺) 2H), 5.11 (dd, J = 8.4, 6.6 Hz, 244.2Hz), 152.64, 1H), 4.94-4.84 (m, 1H), 4.09 135.32 (d, J = 3.3 (dd, J =11.8, 6.6 Hz, 1H), Hz), 130.50 (d, J = 3.92-3.81 (m, 1H), 3.74- 7.8 Hz),127.09 (q, J = 3.65 (m, 1H), 3.60-3.53 (m, 275.9 Hz), 115.17 1H),3.53-3.44 (m, 1H), 3.43- (d, J = 21.2 Hz), 3.33 (m, 1H), 3.17 (t, J =84.96, 83.07, 74.85, 8.6 Hz, 1H), 2.97 (dd, J = 72.42, 71.03, 70.14,13.7, 3.7 Hz, 1H), 2.47-2.34 57.38, 47.05, 34.28, (m, 1H), 2.27-2.13 (m,2H), 1.97- 30.74 (q, J = 29.3 1.89 (m, 1H), 1.89-1.79 Hz), 27.91, 22.99,(m, 2H), 1.49 (s, 18H), 1.46 18.92 (d, J = 6.4 Hz, 3H) F141 — — ESIMS ¹HNMR (CDCl₃) δ 7.18- ¹³C NMR (CDCl₃) δ m/z 589 7.10 (m, 2H), 7.02-6.87(m, 170.15, 161.33 (d, J = ([M + Na]⁺) 2H), 5.03 (t, J = 7.7 Hz, 1H),243.7 Hz), 152.60, 4.91-4.80 (m, 1H), 4.07- 136.06, 130.49 (d, J = 3.96(m, 2H), 3.94-3.83 (m, 7.6 Hz), 115.09 (d, J = 1H), 3.48-3.37 (m, 2H),3.31 21.0 Hz), 83.18, (t, J = 8.0 Hz, 1H), 3.08 (d, J = 83.00, 75.90,72.86, 3.7 Hz, 1H), 2.41-2.29 (m, 71.09, 57.51, 47.32, 1H), 1.87-1.58(m, 8H), 1.48 34.10, 32.67, 32.60, (s, 22H) 27.90, 23.03, 19.02 F142 — —ESIMS ¹H NMR (CDCl₃) δ 7.18- ¹³C NMR (CDCl₃) δ m/z 590 7.11 (m, 2H),7.00-6.91 (m, 169.91, 161.36 (d, J = ([M + Na]⁺) 2H), 5.12 (dd, J = 8.6,6.3 Hz, 243.6 Hz), 152.62, 1H), 4.90-4.81 (m, 1H), 4.13- 135.67 (d, J =3.2 4.04 (m, 1H), 3.85 (dd, J = Hz), 130.56 (d, J = 11.8, 8.6 Hz, 1H),3.63 (dt, J = 7.8 Hz), 115.08 (d, J = 8.7, 6.6 Hz, 1H), 3.56-3.46 21.1Hz), 84.78, (m, 2H), 3.40-3.30 (m, 1H), 83.01, 75.36, 72.74, 3.17-3.02(m, 2H), 2.34 (dd, 72.43, 71.00, 57.43, J = 13.9, 11.4 Hz, 1H), 1.97-47.15, 34.28, 29.98, 1.82 (m, 1H), 1.65-1.54 (m, 28.33, 27.91, 22.57,2H), 1.48 (s, 21H), 1.39-1.29 18.88, 14.00 (m, 4H), 0.94-0.86 (m, 3H)F143 — — ESIMS ¹H NMR (CDCl₃) δ 7.19- ¹⁹F NMR (CDCl₃) m/z 479 7.08 (m,2H), 7.03-6.91 (m, δ −117.2 ([M + Na]⁺) 2H), 5.12 (d, J = 8.3 Hz, 1H),4.95 (dq, J = 9.2, 6.4 Hz, 1H), 4.59 (q, J = 7.5 Hz, 1H), 3.90 (dd, J =11.7, 7.2 Hz, 1H), 3.50-3.20 (m, 5H), 3.16- 3.01 (m, 2H), 2.28 (t, J =12.8 Hz, 1H), 1.94-1.76 (m, 2H), 1.48 (d, J = 6.4 Hz, 3H), 1.42 (s, 9H),0.95 (d, J = 6.7 Hz, 6H) F144 — — ESIMS ¹H NMR (CDCl₃) δ 7.08 (d, J =¹³C NMR (CDCl₃) δ m/z 585 7.9 Hz, 2H), 7.02 (d, J = 8.0 174.27, 169.80,([M + Na]⁺) Hz, 2H), 5.18 (dd, J = 8.7, 5.6 152.58, 136.04, Hz, 1H),5.02-4.89 (m, 2H), 135.66, 129.08, 4.11 (dd, J = 11.9, 5.6 Hz, 128.93,83.06, 77.12, 1H), 3.85 (dd, J = 11.9, 8.8 74.03, 73.63, 71.40, Hz, 1H),3.66 (d, J = 10.7 Hz, 57.69, 45.52, 34.53, 1H), 3.43 (dd, J = 10.8, 6.927.93, 21.00, 18.37, Hz, 1H), 2.70 (dd, J = 14.0, 12.90, 8.57, 8.56 3.8Hz, 1H), 2.31 (s, 3H), 2.25 (dd, J = 13.9, 11.0 Hz, 1H), 2.18-2.02 (m,1H), 1.67- 1.60 (m, 1H), 1.49 (s, 18H), 1.33 (d, J = 5.7 Hz, 3H), 1.07-0.99 (m, 2H), 0.92-0.85 (m, 2H) F145 — — ESIMS ¹H NMR (CDCl₃) δ 7.14-¹³C NMR (CDCl₃) δ m/z 627 7.03 (m, 4H), 5.11 (dd, J = 169.95, 152.62,([M + Na]⁺) 8.5, 6.5 Hz, 1H), 4.94-4.82 136.54, 135.60, (m, 1H),4.12-4.03 (m, 1H), 129.08, 129.00, 3.85 (dd, J = 11.8, 8.5 Hz, 1H),127.11 (q, J = 276.1 3.73-3.63 (m, 1H), 3.61- Hz), 84.97, 83.04, 3.47(m, 2H), 3.45-3.35 74.94, 72.74, 70.96, (m, 1H), 3.17 (t, J = 8.8 Hz,69.97, 57.42, 46.79, 1H), 2.97 (dd, J = 13.7, 3.8 34.67, 30.77 (q, J =Hz, 1H), 2.42-2.32 (m, 1H), 29.0 Hz), 27.91, 22.96 2.32 (s, 3H),2.25-2.13 (m, (q, J = 3.0 Hz), 21.00, 2H), 2.02-1.91 (m, 1H), 1.87-18.94. 1.78 (m, 2H), 1.48 (s, 18H), 1.45 (d, J = 6.3 Hz, 3H) F146 —(Thin Film) HRMS-ESI ¹H NMR (CDCl₃) δ 7.31- — 2979, 2931, (m/z) 7.26 (m,2H), 7.07-6.99 (m, 1742, 1705, [M]⁺ 4H), 6.98-6.92 (m, 3H), 5.16 1491,1392, calcd for (dd, J = 8.5, 6.6 Hz, 1H), 5.10- 1366, 1237, C₃₂H₄₃NO₈,4.99 (m, 1H), 4.30 (t, J = 8.7 1204, 1169, 569.2989; Hz, 1H), 4.12 (dd,J = 11.8, 1142, 1120 found, 6.6 Hz, 1H), 3.90 (dd, J = 569.3001 11.8,8.6 Hz, 1H), 3.60 (d, J = 10.9 Hz, 1H), 3.57-3.46 (m, 1H), 2.97 (dd, J =13.6, 3.3 Hz, 1H), 2.29 (m, 4H), 2.24- 2.13 (m, 1H), 1.49 (s, 18H), 1.38(d, J = 6.4 Hz, 3H) F147 — — ESIMS ¹H NMR (CDCl₃) δ 7.08 (m, ¹³C NMR(CDCl₃) δ m/z 585 4H), 5.03 (t, J = 7.7 Hz, 1H), 170.22, 152.58, ([M +Na]⁺) 4.92-4.81 (m, 1H), 4.10- 137.28, 135.37, 4.02 (m, 1H), 4.02-3.95(m, 1H), 129.03, 83.22, 83.16, 3.93-3.83 (m, 1H), 3.44 82.96, 75.97,73.09, (d, J = 5.3 Hz, 2H), 3.30 (t, J = 71.04, 57.56, 47.11, 8.1 Hz,1H), 3.10 (dd, J = 34.44, 32.70, 32.60, 13.7, 3.7 Hz, 1H), 2.31 27.90,23.04, 23.02, (s, 4H), 1.92-1.81 (m, 1H), 21.01, 19.05 1.81-1.64 (m,5H), 1.47 (m, 24H) F148 — — ESMIS ¹H NMR (CDCl₃) δ 7.53 (d, J = ¹⁹F NMR(CDCl₃) m/z 638 8.0 Hz, 2H), 7.30-7.24 (m, 2H), δ −62.4 ([M + Na]⁺)15.19 (dd, J = 8.7, 5.6 Hz, 1H), 5.01-4.88 (m, 2H), 4.14 (dd, J = 12.0,5.7 Hz, 1H), 3.87 (dd, J = 12.0, 8.7 Hz, 1H), 3.62 (d, J = 11.0 Hz, 1H),3.46 (dd, J = 10.9, 6.5 Hz, 1H), 2.78 (dd, J = 14.0, 4.6 Hz, 1H),2.47-2.32 (m, 1H), 2.22-2.09 (m, 1H), 1.56-1.51 (m, 1H), 1.49 (s, 18H),1.33 (d, J = 5.6 Hz, 3H), 1.02- 0.95 (m, 2H), 0.93-0.82 (m, 2H) F149 — —ESIMS ¹H NMR (CDCl₃) δ 7.53 (d, J = ¹⁹F NMR (CDCl₃) m/z 627 7.8 Hz, 2H),7.31 (d, J = δ −62.4 ([M + Na]⁺) 8.0 Hz, 2H), 5.12 (dd, J = 8.5, 6.4 Hz,1H), 4.93-4.84 (m, 1H), 4.12-4.04 (m, 1H), 3.85 (dd, J = 11.8, 8.5 Hz,1H), 3.51-3.40 (m, 2H), 3.40-3.25 (m, 2H), 3.19-3.09 (m, 2H), 2.44 (t, J= 12.7 Hz, 1H), 2.03-1.93 (m, 1H), 1.93-1.79 (m, 1H), 1.51-1.44 (m,21H), 0.94 (dd, J = 6.7, 1.0 Hz, 6H) F150 — — ESIMS ¹H NMR (CDCl₃) δ7.53 (d, J = ¹⁹F NMR (CDCl₃) m/z 639 8.0 Hz, 2H), 7.31 (d, J = 8.0 δ−62.4 ([M + Na]⁺) Hz, 2H), 5.04 (t, J = 7.7 Hz, 1H), 4.92-4.83 (m, 1H),4.09- 3.97 (m, 2H), 3.94-3.84 (m, 1H), 3.47-3.37 (m, 2H), 3.32 (t, J =8.0 Hz, 1H), 3.17 (dd, J = 13.9, 3.5 Hz, 1H), 2.47 (t, J = 12.8 Hz, 1H),1.95- 1.83 (m, 1H), 1.83-1.61 (m, 6H), 1.55-1.51 (m, 1H), 1.51-1.45 (m,22H) F151 — — ESIMS ¹H NMR (CDCl₃) δ 7.58- ¹⁹F NMR (CDCl₃) m/z 613 7.48(m, 2H), 7.31 (d, J = 8.0 δ −62.3 ([M + Na]⁺) Hz, 2H), 5.12 (dd, J =8.5, 6.3 Hz, 1H), 4.94-4.82 (m, 1H), 4.13-4.05 (m, 1H), 3.90- 3.81 (m,1H), 3.66-3.59 (m, 1H), 3.48 (dt, J = 8.6, 6.6 Hz, 2H), 3.40-3.31 (m,1H), 3.20- 3.10 (m, 2H), 2.45 (t, J = 12.6 Hz, 1H), 2.00 (dd, J = 9.0,4.3 Hz, 1H), 1.65-1.54 (m, 2H), 1.55-1.42 (m, 21H), 0.95 (t, J = 7.4 Hz,3H) F152 — — ESIMS ¹H NMR (CDCl₃) δ 7.58- ¹⁹F NMR (CDCl₃) m/z 641 7.49(m, 2H), 7.26 (d, J = 7.8 δ −62.4 ([M + Na]⁺) Hz, 2H), 5.19 (dd, J =8.7, 5.8 Hz, 1H), 5.04-4.94 (m, 2H), 4.17-4.08 (m, 1H), 3.89 (dd, J =11.9, 8.7 Hz, 1H), 3.64- 3.55 (m, 1H), 3.50-3.42 (m, 1H), 2.74 (dd, J =14.1, 4.0 Hz, 1H), 2.61-2.49 (m, 1H), 2.41 (dd, J = 14.0, 11.2 Hz, 1H),2.19-2.09 (m, 1H), 1.49 (s, 18H), 1.33 (d, J = 5.8 Hz, 3H), 1.19 (appdd, J = 7.0, 2.6 Hz, 6H) F153 — — ESIMS ¹H NMR (CDCl₃) δ 7.57- ¹⁹F NMR(CDCl₃) m/z 641 7.48 (m, 2H), 7.31 (d, J = 8.1 δ −62.3 ([M + Na]⁺) Hz,2H), 5.12 (dd, J = 8.5, 6.3 Hz, 1H), 4.93-4.84 (m, 1H), 4.08 (dd, J =11.9, 6.4 Hz, 1H), 3.85 (dd, J = 11.8, 8.6 Hz, 1H), 3.64 (dt, J = 8.7,6.6 Hz, 1H), 3.57-3.44 (m, 2H), 3.36 (dd, J = 11.0, 5.9 Hz, 1H),3.21-3.10 (m, 2H), 2.45 (t, J = 12.6 Hz, 1H), 2.04- 1.89 (m, 1H),1.64-1.53 (m, 2H), 1.53-1.42 (m, 21H), 1.41-1.27 (m, 4H), 0.94- 0.82 (m,3H) F154 — — ESIMS ¹H NMR (CDCl₃) δ 5.11 (dd, J = ¹⁹F NMR (CDCl₃) m/z551 8.3, 6.7 Hz, 1H), 4.94-4.82 δ −63.3 ([M + Na]⁺) (m, 1H), 4.23-4.15(m, 1H), 3.93 (dd, J = 11.9, 8.3 Hz, 1H), 3.75-3.59 (m, 2H), 3.37 (dd, J= 8.4, 6.4 Hz, 1H), 3.18 (dd, J = 8.4, 6.4 Hz, 1H), 3.11 (t, J = 8.5 Hz,1H), 2.44-2.28 (m, 1H), 2.28-2.13 (m, 1H), 2.10-2.01 (m, 1H), 1.88- 1.77(m, 1H), 1.51 (s, 18H), 1.45 (d, J = 6.5 Hz, 3H), 0.91 (d, J = 6.6 Hz,6H) F155 — — ESIMS ¹H NMR (CDCl₃) δ 5.04- ¹⁹F NMR (CDCl₃) m/z 562 4.96(m, 1H), 4.89 (q, J = 6.8 δ −63.7 ([M + Na]⁺) Hz, 1H), 4.20-4.10 (m,1H), 4.05-3.90 (m, 2H), 3.78- 3.69 (m, 1H), 3.68-3.59 (m, 1H), 2.29-2.15(m, 1H), 3.27 (t, J = 7.1 Hz, 1H), 2.52-2.35 (m, 1H), 2.03-1.94 (m, 1H),1.78-1.61 (m, 5H), 1.59- 1.48 (m, 21H), 1.44 (d, J = 6.6 Hz, 3H) F156 —— ESIMS ¹H NMR (CDCl₃) δ 5.14 (dd, J = ¹³C NMR (CDCl₃) δ m/z 539 8.5,5.7 Hz, 1H), 4.89-4.78 169.75, 152.67, 84.31, ([M + Na]⁺) (m, 1H), 4.18(dd, J = 11.9, 82.96, 78.41, 75.49, 5.7 Hz, 1H), 3.89 (dd, J = 71.64,57.84, 45.24, 11.9, 8.5 Hz, 1H), 3.71-3.64 35.99, 29.12, 28.41, (m, 1H),3.45 (dd, J = 10.9, 27.94, 26.61, 22.75, 6.4 Hz, 1H), 3.31 (dd, J = 8.3,22.43, 19.49, 19.02 6.5 Hz, 1H), 3.24 (dd, J = 8.3, 6.3 Hz, 1H), 3.02(t, J = 8.9 Hz, 1H), 1.89-1.78 (m, 1H), 1.68-1.45 (m, 20H), 1.42 (d, J =6.3 Hz, 3H), 1.35-1.05 (m, 4H), 0.91 (d, J = 6.7 Hz, 6H), 0.87 (app dd,J = 6.6, 2.6 Hz, 6H) F157 — — ESIMS ¹H NMR (CDCl₃) δ 5.14 (dd, J = ¹⁹FNMR (CDCl₃) m/z 593 8.5, 5.9 Hz, 1H), 4.89-4.79 δ −66.4 ([M + Na]⁺) (m,1H), 4.19 (dd, J = 11.9, 5.9 Hz, 1H), 3.90 (dd, J = 12.0, 8.5 Hz, 1H),3.71-3.57 (m, 2H), 3.57-3.43 (m, 2H), 3.06 (t, J = 8.8 Hz, 1H), 2.26-2.12 (m, 2H), 1.86-1.76 (m, 2H), 1.65 (s, 2H), 1.51 (s, 18H), 1.41 (d, J= 6.3 Hz, 3H), 1.35-1.02 (m, 4H), 0.88 (dd, J = 6.6, 4.0 Hz, 6H) F158 —— ESIMS ¹H NMR (CDCl₃) δ 5.22 (dd, J = ¹³C NMR (CDCl₃) δ m/z 550 8.7,4.8 Hz, 1H), 4.96-4.81 174.09, 169.53, ([M + Na]⁺) (m, 2H), 4.23 (dd, J= 12.0, 152.64, 83.02, 76.56, 4.9 Hz, 1H), 3.91 (dd, J = 76.20, 74.16,72.12, 12.0, 8.8 Hz, 1H), 3.80 (dd, J = 58.02, 44.11, 35.18, 10.8, 1.3Hz, 1H), 3.50 (dd, J = 28.23, 27.94, 27.02, 10.8, 7.3 Hz, 1H), 1.83-22.68, 22.16, 18.40, 1.73 (m, 1H), 1.65-1.58 (m, 12.86, 8.42, 8.33 1H),1.51 (s, 18H), 1.48-1.38 (m, 1H), 1.29 (d, J = 5.9 Hz, 3H), 1.28-1.11(m, 1H), 1.22- 1.11 (m, 2H), 1.09-0.98 (m, 3H), 0.93-0.87 (m, 2H),0.86-0.81 (m, 6H) F159 — (Thin Film) HRMS-ESI ¹H NMR (CDCl₃) δ 7.10- —2954, 2932, (m/z) 7.01 (m, 2H), 6.84-6.76 (m, 2870, 1743, [M]⁺ 2H), 5.18(dd, J = 8.5, 5.8 Hz, 1706, 1507, calcd for 1H), 5.04-4.94 (m, 1H), 4.231392, 1365, C₃₀H₄₇NO₈, (dd, J = 11.9, 5.9 Hz, 1H), 1235, 1167, 549.3302;4.13 (t, J = 8.9 Hz, 1H), 3.95 1144, 1118 found, (dd, J = 11.9, 8.5 Hz,1H), 549.3322 3.74 (dd, J = 11.0, 1.5 Hz, 1H), 3.58 (dd, J = 11.0, 6.8Hz, 1H), 2.28 (s, 3H), 1.91- 1.78 (m, 1H), 1.56-1.45 (m, 20H), 1.34 (d,J = 6.4 Hz, 3H), 1.22- 1.04 (m, 3H), 0.77 (d, J = 6.6 Hz, 3H), 0.73 (d,J = 6.6 Hz, 3H) F160 — — — ¹H NMR (CDCl₃) δ 5.15 (dd, J = ¹³C NMR(CDCl₃) δ 8.5, 5.7 Hz, 1H), 4.87-4.78 (m, 169.74, 152.65, 84.57, 1H),4.18 (dd, J = 11.9, 5.7 Hz, 82.95, 75.51, 73.54, 1H), 3.89 (dd, J =11.9, 8.5 Hz, 71.61, 57.81, 45.23, 1H), 3.71-3.63 (m, 1H), 3.55-3.3835.94, 28.37, 27.93, (m, 3H), 3.03 (t, J = 9.0 Hz, 26.70, 23.43, 22.76,1H), 1.67-1.52 (m, 5H), 1.50 (s, 22.38, 18.97, 10.69 18H), 1.43 (d, J =6.4 Hz, 3H), 1.36- 1.04 (m, 3H), 0.93 (t, J = 7.4 Hz, 3H), 0.88 (d, J =3.1 Hz, 3H), 0.87 (d, J = 3.1 Hz, 3H) F161 — — ESIMS ¹H NMR (CDCl₃) δ5.04 (t, J = ¹³C NMR (CDCl₃) δ m/z 551 7.4 Hz, 1H), 4.86-4.75 (m,169.95, 152.63, 83.27, ([M + Na]⁺) 1H), 4.14 (dd, J = 11.8, 7.1 82.94,82.87, 76.01, Hz, 1H), 4.00-3.92 (m, 2H), 75.71, 71.67, 57.88, 3.62-3.50(m, 2H), 3.18 (t, J = 45.58, 36.81, 32.61, 8.1 Hz, 1H), 1.77-1.59 32.52,28.41, 27.92, (m, 7H), 1.56-1.46 (m, 22H), 26.45, 23.08, 23.05, 1.43 (d,J = 6.5 Hz, 3H), 1.36- 22.73, 22.47, 19.05 1.22 (m, 1H), 1.19-1.05 (m,2H), 0.90-0.80 (m, 6H) F162 — — ESIMS ¹H NMR (CDCl₃) δ 6.85- ¹⁹F NMR(CDCl₃) m/z 512 6.73 (m, 2H), 5.16 (d, J = δ −134.8 (dd, J = ([M + Na]⁺)8.3 Hz, 1H), 5.02-4.89 (m, 20.9, 9.2 Hz), −163.9-−164.2 1H), 4.63-4.52(m, 1H), 4.00- (m) 3.87 (m, 1H), 3.50-3.22 (m, 5H), 3.13-2.97 (m, 2H),2.37- 2.21 (m, 1H), 1.93-1.74 (m, 2H), 1.51-1.45 (d, J = 6.3 Hz, 3H),1.45-1.37 (s, 9H), 1.00- 0.89 (m, 6H) F163 — — ESIMS ¹H NMR (CDCl₃) δ7.34 (d, J = ¹³C NMR (CDCl₃) δ m/z 641 1.7 Hz, 1H), 7.19-7.13 (m, 2H),176.32, 169.77, ([M + Na]⁺) 5.17 (dd, J = 8.6, 6.2 Hz, 1H), 152.61,135.36, 5.02-4.92 (m, 2H), 4.13 (dd, J = 134.93, 132.83, 11.8, 6.2 Hz,1H), 3.90 (dd, 132.45, 129.41, J = 11.8, 8.7 Hz, 1H), 3.5- 126.99,83.12, 77.23, 3.44 (m, 2H), 2.78 (dd, J = 73.78, 71.17, 57.40, 13.8, 3.6Hz, 1H), 2.59 (h, J = 43.77, 34.22, 32.23, 7.0 Hz, 1H), 2.46 (t, J =27.91, 19.03, 18.94, 12.8 Hz, 1H), 2.16 (bs, 1H), 18.30 1.49 (s, 18H),1.33 (d, J = 5.9 Hz, 3H), 1.22-1.20 (m, 6H) F164 — — ESIMS ¹H NMR(CDCl₃) δ 7.35 (d, J = — m/z 628 2.1 Hz, 1H), 7.23-7.15 (m, ([M + Na]⁺)2H), 5.11 (dd, J = 8.4, 6.6 Hz, 1H), 4.89 (dd, J = 8.8, 6.4 Hz, 1H),4.07 (dd, J = 11.8, 6.5 Hz, 1H), 3.87 (dd, J = 11.8, 8.5 Hz, 1H),3.46-3.28 (m, 3H), 3.19-3.11 (m, 2H), 2.54 (t, J = 12.9 Hz, 1H), 2.05(bs, 1H), 1.86 (dp, J = 13.2, 6.6 Hz, 1H), 1.52-1.46 (m, 4H), 1.48 (s,18H), 0.93 (d, J = 6.7 Hz, 6H) F165 — — ESIMS ¹H NMR (CDCl₃) δ 7.35 (d,J = — m/z 641 2.1 Hz, 1H), 7.25-7.06 (m, ([M + Na]⁺) 2H), 5.11 (dd, J =8.3, 6.6 Hz, 1H), 4.88 (dd, J = 8.9, 6.4 Hz, 1H), 4.07 (dd, J = 11.8,6.6 Hz, 1H), 3.87 (dd, J = 11.8, 8.5 Hz, 1H), 3.70-3.59 (m, 1H),3.55-3.49 (m, 1H), 3.46-3.27 (m, 2H), 3.24-3.08 (m, 2H), 2.55 (t, J =12.8 Hz, 1H), 2.08-1.98 (m, 1H), 1.65- 1.29 (m, 9H), 1.48 (s, 18H), 0.89(t, J = 7.0 Hz, 3H) F166 — — ESIMS ¹H NMR (CDCl₃) δ 7.31 (d, J = — m/z539 1.8 Hz, 1H), 7.17-7.11 ([M − t-BOC]⁺) (m, 2H), 7.08 (d, J = 8.2 Hz,2H), 6.85 (d, J = 8.6 Hz, 2H), 5.16 (dd, J = 8.3, 6.9 Hz, 1H), 5.05 (dq,J = 8.5, 6.4 Hz, 1H), 4.27 (t, J = 8.6 Hz, 1H), 4.13 (dd, J = 11.8, 6.8Hz, 1H), 3.93 (dd, J = 11.8, 8.5 Hz, 1H), 3.58- 3.43 (m, 2H), 3.04 (dd,J = 13.7, 3.5 Hz, 1H), 2.52 (t, J = 12.7 Hz, 1H), 2.33-2.19 (m, 1H),2.28 (s, 3H), 1.49 (s, 18H), 1.39 (d, J = 6.4 Hz, 3H) F167 — — ESIMS ¹HNMR (CDCl₃) δ 5.20 (dd, J = — m/z 565 8.6, 5.7 Hz, 1H), 4.96-4.89 ([M +Na]⁺) (m, 1H), 4.79 (t, J = 9.0 Hz, 1H), 4.23 (dd, J = 11.9, 5.7 Hz,1H), 3.93 (dd, J = 11.9, 8.7 Hz, 1H), 3.75 (d, J = 10.7 Hz, 1H), 3.56(dd, J = 10.9, 7.1 Hz, 1H), 2.56 (h, J = 7.0 Hz, 1H), 1.91-1.42 (m, 8H),1.51 (s, 18H), 1.29 (d, J = 6.3 Hz, 3H), 1.19 (d, J = 7.0 Hz, 6H), 1.13-0.93 (m, 4H) F168 — — ESIMS ¹H NMR (CDCl₃) δ 5.11 (dd, J = — m/z 5518.3, 6.5 Hz, 1H), 4.89-4.78 ([M + Na]⁺) (m, 1H), 4.18 (dd, J = 11.8, 6.4Hz, 1H), 3.91 (dd, J = 11.8, 8.4 Hz, 1H), 3.62 (d, J = 10.7 Hz, 1H),3.51 (dd, J = 10.9, 6.3 Hz, 1H), 3.33 (dd, J = 8.3, 6.3 Hz, 1H), 3.21(dd, J = 8.3, 6.6 Hz, 1H), 2.97 (t, J = 8.7 Hz, 1H), 2.88 (t, J = 7.6Hz, 2H), 2.71 (t, J = 7.6 Hz, 2H), 1.97-1.45 (m, 6H), 1.50 (s, 18H),1.42 (d, J = 6.4 Hz, 3H), 1.32-1.22 (m, 1H), 1.15- 1.00 (m, 2H), 0.91(dd, J = 6.7, 4.2 Hz, 6H) F169 — — ESIMS — — m/z 565 ([M + Na]⁺) F170 —— ESIMS ¹H NMR (CDCl₃) δ 7.07 (m, ¹³C NMR (CDCl₃) δ m/z 473 4H), 5.14(d, J = 8.2 Hz, 1H), 172.24, 154.95, ([M + Na]⁺) 4.95 (dq, J = 9.2, 6.4Hz, 1H), 136.81, 135.52, 4.59 (q, J = 7.3 Hz, 1H), 3.87 129.10, 129.01,84.66, (dd, J = 11.5, 7.3 Hz, 1H), 80.02, 79.21, 75.57, 3.44 (t, J = 7.4Hz, 2H), 3.31 72.86, 72.48, 52.97, (dddd, J = 24.1, 18.8, 10.5, 6.847.40, 34.56, 29.17, Hz, 3H), 3.10 (dd, J = 10.4, 28.27, 21.01, 19.48,6.6 Hz, 2H), 2.31 (s, 3H), 2.24 18.80 (t, J = 12.7 Hz, 1H), 1.87 (dt, J= 13.2, 6.6 Hz, 2H), 1.47 (d, J = 6.4 Hz, 3H), 1.41 (s, 9H), 0.95 (d, J= 6.7 Hz, 6H) F171 — — ESIMS — — m/z 362 ([M + H]⁺) F172 — — ESIMS — —m/z 404 ([M + H]⁺) F173 — — ESIMS — — m/z 364 ([M + H]⁺) F174 — — ESIMS— — m/z 350 ([M + H]⁺) F175 — — ESIMS — — m/z 400 ([M + H]⁺) F176 — —ESIMS — — m/z 440 ([M + H]⁺) F177 — — ESIMS — — m/z 401 ([M + H]⁺) F178— — ESIMS — — m/z 420 ([M + H]⁺) F179 — — ESIMS — — m/z 398 ([M + H]⁺)F180 — — ESIMS — — m/z 404 ([M + H]⁺) F181 — — ESIMS — — m/z 364 ([M +H]⁺) F182 — — ESIMS — — m/z 364 ([M + H]⁺) F183 — — ESIMS — — m/z 366([M + H]⁺) F184 — — ESIMS — — m/z 368 ([M + H]⁺) F185 — — HRMS-ESI — —(m/z) [M + H]⁺ calcd for C₂₀H₂₈NO₅, 362.1962; found, 362.1956 F186 — — —— — F187 — — HRMS-ESI — — (m/z) [M]⁺ calcd for C₁₉H₂₅F₄NO₄, 407.172;found, 407.1726 F188 — — HRMS-ESI — — (m/z) [M + H]⁺ calcd forC₂₀H₂₉FNO₄, 366.2075; found, 366.2082 F189 — — ESIMS — — m/z 368 ([M +H]⁺) F190 — — ESIMS — — m/z 374 ([M + H]⁺) F191 — — ESIMS — — m/z 354([M + H]⁺) F192 — — HRMS-ESI — — (m/z) [M + H]⁺ calcd for C₂₀H₂₈NO₅,362.1962; found, 362.1963 F193 — — HRMS-ESI — — (m/z) [M]⁺ calcd forC₂₀H₂₈F₃NO₄, 403.1970; found, 403.1973 F194 — — — — F195 — — ESIMS — —m/z 362 ([M + H]⁺) F196 — — — — F197 — — ESIMS — — m/z 404 ([M + H]⁺)F198 — — ESIMS — — m/z 416 ([M + H]⁺) F199 — — ESIMS — — m/z 390 ([M +H]⁺) F200 — — ESIMS — — m/z 418 ([M + H]⁺) F201 — — ESIMS — — m/z 418([M + H]⁺) F202 — — ESIMS — — m/z 328 ([M + H]⁺) F203 — — ESIMS — — m/z340 ([M + H]⁺) F204 — — ESIMS — — m/z 316 ([M + H]⁺) F205 — — HRMS-ESI —— (m/z) [M]⁺ calcd for Cl₇H₃₀F₃NO₄, 369.2127; found, 369.2126 F206 — —HRMS-ESI — — (m/z) [M]⁺ calcd for Cl₇H₂₉NO₅, 327.2046; found, 327.2053F207 — — HRMS-ESI — — (m/z) [M]⁺ calcd for C₂₀H₃₁NO₄, 349.2253; found,349.2240 F208 — — ESIMS — — m/z 302 ([M + H]⁺) F209 — — ESIMS — — m/z328 ([M + H]⁺) F210 — — HRMS-ESI — — (m/z) [M]⁺ calcd for Cl₉H₂₆F₃NO₄,389.1814; found, 389.1831 F211 — — ESIMS ¹H NMR (DMSO-d₆) δ 8.51 — m/z419 (bs, 3H), 7.61 (d, J = 2.1 Hz, ([M + H]⁺) 1H), 7.40 (dd, J = 8.3,2.1 Hz, 1H), 7.35 (d, J = 8.3 Hz, 1H), 5.08-5.00 (m, 1H), 4.89 (t, J =9.4 Hz, 1H), 4.47-4.44 (m, 1H), 3.95 (dd, J = 12.4, 7.0 Hz, 1H),3.65-3.45 (m, 3H), 2.71 (dd, J = 13.8, 3.7 Hz, 1H), 2.64 (p, J = 7.0 Hz,1H), 2.38-2.32 (m, 1H), 2.11- 2.01 (m, 1H), 1.27 (d, J = 6.3 Hz, 3H),1.15 (d, J = 7.0 Hz, 6H) F212 — — ESIMS — — m/z 404.3 ([M + H]⁺) F213 —— ESIMS — — m/z 418.23 ([M + H]⁺) F214 — — ESIMS — — m/z 438.2 ([M +H]⁺) F215 — — HRMS-ESI — — (m/z) [M]⁺ calcd for Cl₈H₃₁NO₅, 341.2202;found, 341.2201 F216 — — ESIMS — — m/z 328.4 ([M + H]⁺) F217 — — ESIMS —— m/z 342.4 ([M + H]⁺) F218 81-84 — ESIMS ¹H NMR (CDCl₃) δ 7.08 (t, J =— m/z 351 2.7 Hz, 4H), 4.91 (dq, J = ([M + H]⁺) 9.2, 6.4 Hz, 1H), 3.84(dd, J = 11.6, 7.5 Hz, 1H), 3.76 (m, 1H), 3.71 (d, J = 7.7 Hz, 1H), 3.64(m, 1H), 3.47 (dd, J = 8.3, 6.4 Hz, 1H), 3.41 (dd, J = 10.7, 6.1 Hz,1H), 3.31 (m, 2H), 3.13 (d, J = 9.0 Hz, 1H), 3.09 (m, 1H), 3.04 (m, 2H),2.31 (s, 3H), 1.87 (m, 2H), 1.61 (s, 1H), 1.47 (d, J = 6.4 Hz, 3H), 0.95(dd, J = 6.7, 1.6 Hz, 6H) ^(*1)H NMR were run at 400 MHz unless notedotherwise *¹³C NMR were run at 101 MHz unless noted otherwise *¹⁹F NMRwere run at 376 MHz unless noted otherwise

TABLE 3 Biological Testing Rating Scale Rating Table for FungalPathogens % Control Rating 80-100 A More than 0-Less than 80 B NotTested C No activity noticed in this bioassay D

TABLE 4 Biological Activity - Disease Control in High and Low VolumeApplications PUCCRT* SEPTTR* 1DP* 3DC* 1DP* 3DC* Rate Rate Cmpd. 121.5100 121.5 100 121.5 100 121.5 100 No. g/H* ppm* g/H* ppm* g/H* ppm* g/H*ppm* F1 C A C A C A C B F2 C A C B C A C A F3 C A C A C A C A F4 C A C AC A C A F5 C B C B C A C B F6 C B C D C A C B F7 C A C B C A C B F8 C AC B C A C B F9 C A C D C A C A F10 C A C D C A C B F11 C A C B C A C AF12 C A C A C A C A F13 C A C A C A C A F14 C A C A C A C A F15 C A C BC A C A F16 C A C B C A C B F17 C A C B C A C A F18 C A C A C A C B F19C A C A C A C A F20 C C C C C C C C F21 C A C A C A C A F22 C B C B C DC B F23 C A C B C A C B F24 C A C B C A C B F25 C A C B C A C A F26 C BC D C A C B F27 C A C B C A C B F28 C A C B C A C B F29 C A C B C A C AF30 C A C D C A C B F31 C B C D C A C B F32 C A C B C A C B F33 C B C DC A C B F34 C A C A C A C A F35 C A C D C A C B F36 C A C B C A C A F37C A C B C A C A F38 C A C A C A C A F39 C A C A C A C A F40 C B C D C AC A F41 C A C D C A C A F42 C A C A C A C A F43 C B C D C A C B F44 C AC D C D C D F45 C A C B C A C A F46 C A C A C A C A F47 C A C A C A C AF48 C A C A C A C B F49 A A B A A A A A F50 C A C A C A C A F51 C A C BC A C A F52 C A C B C A C A F53 A A B A A A B A F54 A A B A A A A A F55C A C A C A C A F56 C A C A C A C A F57 A A B A A A A A F58 A A B A A AA A F59 A A B A A A A A F60 A A A A A A A A F61 A A B A A A B A F62 A AB A A A A A F63 A A B A A A A A F64 C A C A C A C A F65 A A B A A A A AF66 A A B B A A B B F67 C A C A C A C B F68 A A A A A A A A F69 A A B AA A A A F70 C A C A C A C A F71 C A C A C A C A F72 A A A A A A A A F73A A B A A A A A F74 C A C A C A C A F75 A A B A A A A A F76 A A B D A BD D F77 A A A A A A A A F78 C A C A C A C A F79 A A B A A A A A F80 A AA A A A A A F81 C A C A C A C A F82 A A A A A A A A F83 A A B A B A A AF84 C A C A C A C D F85 C A C B C A C B F86 C A C A C A C A F87 A A B AA A A A F88 C A C A C A C A F89 C A C A C A C A F90 C A C A C A C A F91C A C A C A C A F92 A A A A A A A A F93 A A A A A A A A F94 A A A A A AA A F95 C A C A C A C A F96 A A A A A A A A F97 A A A A A A A B F98 A AB A A A B A F99 A A B A A A A A F100 A A B A A A B A F101 C A C A C A CA F102 C A C A C A C A F103 C A C A C A C B F104 A A A A A A A A F105 AA A A A A A A F106 A A A A A A A A F107 A A A A A A A A F108 A A A A A AA A F109 A A A A A A A A F110 A A B A A A A A F111 C A C A C A C A F112A C B C A C A C F113 A C D C D C D C F114 A A A A A A A A F115 A A A A AA A A F116 A A A A A A A A F117 A A A A A A A A F118 A A A A A A A AF119 C A C A C A C A F120 C A C B C A C A F121 A A A A A A A A F122 A CB C A C D C F123 A C D C A C D C *PUCCRT—Wheat Brown Rust (Pucciniatriticina) *SEPTTR—Wheat Leaf Blotch (Septoria tritici) *1DP—1 DayProtectant *3DC—3 Day Curative

TABLE 5 Biological Activity - Disease Control at 100 ppm Com- pound.ALTESO* CERCBE* COLLLA* ERYSCI* ERYSGH* Number 1DP* F60 C A C A C F73 BA A B C F80 A A A A A F82 B B A B C F83 D A A D A F96 A A A A A F105 B AA B C F107 A A C A B F108 A A C A A F110 A A A B C F114 A A A A A F117 AA A A A F122 A A A B A F123 A A A A A *ALTESO—Tomato Early Blight(Alternaria solani) *CERCBE—Leaf Spot of Sugar Beets (Cercosporabeticola) *COLLLA—Cucumber Anthracnose (Glomerella lagenarium; Anamorph:Colletotricum lagenarium) *ERYSCI—Powdery Mildew of Cucumber (Erysiphecichoracearum) *ERYSGH—Barley Powdery Mildew (Blumeria graminis f.sp.hordei; Synonym: Erysiphe graminis f.sp. hordei) *1DP—1 Day Protectant

TABLE 6 Biological Activity - Disease Control at 100 ppm Compound.ERYSGT* LEPTNO* PYRIOR* RHYNSE* UNCINE* VENTIN* Number 1DP* F60 C C C CA C F73 C C A A C C F80 A A A C B B F82 C C A A C C F83 C A A A B A F96A A A C A C F105 C C A A C C F107 C C A A B C F108 C C A A A C F110 C CA A C C F114 C C A A A A F117 A A A C A A F122 C A C A A A F123 C A C AA B *ERYSGT—Wheat Powdery Mildew (Blumeria graminis f.sp. tritici;Synonym: Erysiphe graminis f.sp. tritici) *LEPTNO—Wheat Glume Blotch(Leptosphaeria nodorum) *PYRIOR—Rice Blast (Magnaporthe grisea;Anamorph: Pyricularia oryzae) *RHYNSE—Barley Scald (Rhyncosporiumsecalis) *UNCINE—Grape Powdery Mildew (Uncinula necator) *VENTIN—AppleScab (Venturia inaequalis) *1DP—1 Day Protectant

TABLE 7 Biological Activity - Disease Control at 25 ppm Compound PHAKPA*Number 1DP* 3DC* F106 A A F107 A B F108 A A F109 A B F114 A B F122 B DF123 B D *PHAKPA—Asian Soybean Rust (Phakopsora pachyrhizi) *1DP—1 DayProtectant *3DC—3 Day Curative

What is claimed:
 1. A compound of Formula I

wherein: X is H or C(O)R₃; Y is H, C(O)R₃, or Q; Q is

R₁ is chosen from H, alkyl, alkenyl, aryl, —Si(R₆)₃, or —C(O)R₆, eachoptionally substituted with 0, 1 or multiple R₅; R₂ is chosen from H,alkyl, aryl, heteroaryl, or arylalkyl, each optionally substituted with0, 1 or multiple R₅; R₃ is chosen from alkoxy, or benzyloxy, eachoptionally substituted with 0, 1, or multiple R₅; R₄ is chosen from H,—C(O)R₇, or —CH₂OC(O)R₇; R₅ is chosen from H, alkyl, alkenyl, halo,haloalkyl, alkoxy, aryl, heteroaryl, heterocyclyl, or —C(O)R₆; R₆ ischosen from alkyl, alkenyl, haloalkyl, alkoxy, aryl or heteroaryl; andR₇ is chosen from alkyl or alkoxy, each optionally substituted with 0,1, or multiple R₆; with the proviso that R₂ is not unsubstituted phenylor unsubstituted cyclohexyl.
 2. The compound according to claim 1,wherein X and Y are independently chosen from H or C(O)R₃.
 3. Thecompound according to claim 2, wherein R₁ is chosen from H, alkyl,alkenyl, aryl, —Si(R₆)₃, or —C(O)R₆, each optionally substituted with 0,1 or multiple R₅.
 4. The compound according to claim 3, wherein R₂ ischosen from H, alkyl, aryl, heteroaryl, or arylalkyl, each optionallysubstituted with 0, 1 or multiple R₅.
 5. The compound according to claim1, wherein X is H and Y is Q.
 6. The compound according to claim 5,wherein R₁ is chosen from H, alkyl, alkenyl, aryl, —Si(R₆)₃, or —C(O)R₆,each optionally substituted with 0, 1 or multiple R₅.
 7. The compoundaccording to claim 6, wherein R₂ is chosen from H, alkyl, aryl,heteroaryl, or arylalkyl, each optionally substituted with 0, 1 ormultiple R₅.
 8. The compound according to claim 7, wherein R₄ is H,—C(O)R_(D), or —CH₂OC(O)R₇.
 9. The compound according to claim 8,wherein R₇ is alkyl or alkoxy, each optionally substituted with 0, 1, ormultiple R₆.
 10. A formulation for the control of a fungal pathogen,comprising: at least one of the compounds of claim 1; and aphytologically acceptable carrier material.
 11. The formulationaccording to claim 10, wherein the formulation is suitable for treatingplants.
 12. A formulation for the control of a fungal pathogen,comprising: at least one of the compounds of claim 1; and at least oneagriculturally active ingredient selected from the group consisting of:fungicides, insecticides, nematocides, miticides, arthropodicides,bactericides and combinations thereof.
 13. The formulation according toclaim 12, wherein the formulation is suitable for treating plants.
 14. Aformulation for the control of a fungal pathogen, comprising: theformulation of claim 10; and at least one agriculturally activeingredient selected from the group consisting of: fungicides,insecticides, nematocides, miticides, arthropodicides, bactericides andcombinations thereof.
 15. The formulation according to claim 14, whereinthe formulation is suitable for treating plants.